bluuebunny/crossref_metadata_2025 huggingface dataset:
Active learning: in context.
Authors: Rangachari P K
Published: December 2017

Active learning has become trendy, particularly in health care education. It has been noted that active learning is an attitude, not a method. Promotion of active learning requires willing students, sympathetic teachers, and an institution willing to promote interactions between them. The essence is to shift the locus of control from the teacher to the student. This essay draws attention to books and articles discussing such issues.
Muscle chamber with strain gauge adapted for isotonic/isometric recording.
Authors: Easton D M
Published: December 2017

Simple devices are described that can facilitate student experiments on mechanical and electrical aspects of muscle contraction, for example, of isolated preparations such as frog gastrocnemius and sartorius muscles and gut. The system includes a general-purpose preparation bath that was previously described for electrophysiological observations with suction electrodes [D.M. Easton. Am.J. Physiol. 265 (Adv. Physiol.Educ. 10): S35-S46, 1993]. A tower installed in the bath allows the muscle to be oriented vertically but completely submerged in a limited volume. Recording of isotonic contraction, which is the more familiar behavior of skeletal muscle, is made convenient by an accessory to convert the commonly available Statham force transducer to isometric recording. Phenomena not conveniently accessible by isometric recording, such as muscle work, and also the length-tension relation, not ordinarily observed for isotonic contraction, can be demonstrated.
Teaching nerve conduction to undergraduates: the "traveling flame" analogy revisited.
Authors: Sircar S S , Tandon O P
Published: December 2017

A familiar analogy to the propagation of the electric wave in a nerve lies in the burning of a cigarette. This analogy, which has persisted through several editions of popular textbooks of physiology, has never been elaborated beyond a cursory mention. In this article, the analogy is reinvoked and refined to explain the cable properties of nerve, saltatory conduction, and some other factors affecting nerve conduction velocity. Experience in lecture classes and feedback obtained through class tests indicate that the analogy, if suitably elaborated and judiciously applied, can increase the retention of the subject by the students.
Cooperative quizzes in the anatomy and physiology laboratory: a description and evaluation.
Authors: Jensen M S
Published: December 2017

Physiology educators read journals, such as this one, to gather ideas about curriculum and instruction. Most articles focus on curriculum (i.e., what is taught), but this paper will focus on instruction (i.e., how curriculum is implemented). Just as there are different types of curricula, there are different types of instruction. The most common strategy is lecture. Lectures are extremely efficient for delivering large amounts of information in a short period of time. A common laboratory strategy is discovery or inquiry-based learning (i.e., giving students tools, cognitive and physical, to deduce new information via investigations). A third instructional strategy is the use of cooperative learning. Proper conditions are required for each instructional strategy, and problems arise when the wrong combinations are put together. This paper will describe how a cooperative learning environment can be created in the anatomy and physiology laboratory through the use of cooperative quizzes. It will include a brief introduction to the pedagogical theory behind cooperative learning and an evaluation of the effectiveness of quizzes compared with more traditional methods.
A comparison of methods for dealing with troublesome examination questions.
Authors: Norton J M
Published: December 2017

This study compared two methods for identifying troublesome examination questions: a postexam student "challenge committee" process and a "question citation" procedure allowing students to identify troublesome questions during an exam. Challenged and cited questions on eight examinations given to second-year medical students were compared with respect to the percentage of correct responses (%CR) and the discrimination index (DI). Challenged questions had a significantly lower mean value for %CR (53.2 +/- 22.5, n = 74) than unchallenged questions (84.7 +/- 15.4, n = 428) but the two groups did not differ with respect to DI. For cited questions, the number of citations was correlated with %CR (r = -0.5480, p < 0.001) but not with DI. The group of questions that received three or more citations (n = 145) included 67.6% of all challenged questions and 78.3% of challenges that eventually led to a change in an answer key. A simple citation procedure completed during an exam could replace a complicated, post-exam challenge committee process and achieve the same goal of identifying troublesome questions.
Teaching physiology and the World Wide Web: electrochemistry and electrophysiology on the Internet.
Authors: Dwyer T M , Fleming J , Randall J E , Coleman T G
Published: December 2017

Students seek active learning experiences that can rapidly impart relevant information in the most convenient way possible. Computer-assisted education can now use the resources of the World Wide Web to convey the important characteristics of events as elemental as the physical properties of osmotically active particles in the cell and as complex as the nerve action potential or the integrative behavior of the intact organism. We have designed laboratory exercises that introduce first-year medical students to membrane and action potentials, as well as the more complex example of integrative physiology, using the dynamic properties of computer simulations. Two specific examples are presented. The first presents the physical laws that apply to osmotic, chemical, and electrical gradients, leading to the development of the concept of membrane potentials; this module concludes with the simulation of the ability of the sodium-potassium pump to establish chemical gradients and maintain cell volume. The second module simulates the action potential according to the Hodgkin-Huxley model, illustrating the concepts of threshold, inactivation, refractory period, and accommodation. Students can access these resources during the scheduled laboratories or on their own time via our Web site on the Internet (http./(/)phys-main.umsmed.edu) by using the World Wide Web protocol. Accurate version control is possible because one valid, but easily edited, copy of the labs exists at the Web site. A common graphical interface is possible through the use of the Hypertext mark-up language. Platform independence is possible through the logical and arithmetic calculations inherent to graphical browsers and the Javascript computer language. The initial success of this program indicates that medical education can be very effective both by the use of accurate simulations and by the existence of a universally accessible Internet resource.
"Virtual" experiment for understanding the electrocardiogram and the mean electrical axis.
Authors: Anderson J , DiCarlo S E
Published: December 2017

Educators have placed an emphasis on the development of laboratory materials that supplement the traditional lecture format. The laboratory materials should encourage active learning, small group discussion, and problem-solving skills. To this end, we developed a virtual experiment designed to introduce students to the theory and application of the electrocardiogram (ECG) and the mean electrical axis (MEA). After reviewing background material, the students will analyze ECG recordings from two individuals who underwent a series of experimental procedures. The students are challenged to reduce and analyze the data, calculate and plot the MEA, and answer questions related to the theory and application of the ECG. In conducting the virtual experiment, students are introduced to inquiry-based learning through experimentation.
Quantitative concept mapping in pulmonary physiology: comparison of student and faculty knowledge structures.
Authors: McGaghie W C , McCrimmon D R , Mitchell G , Thompson J A , Ravitch M M
Published: December 2017

Quantitative concept mapping, in contrast with qualitative approaches, is rigorous scientifically and permits statistical analyses of data about concept learning. This study extends past quantitative research on the structure of student concept learning in pulmonary physiology. Pathfinder scaling is used to derive concept maps for medical and veterinary students and their physiology instructors at Northwestern University and the University of Wisconsin, respectively. The concept maps are evaluated for coherence (internal consistency), student-instructor similarity, and correlation of similarity with final examination scores. Results show that student and instructor concept maps are coherent and that student concept maps become increasingly similar to instructors' concept maps from pre- to postinstruction, but that student-instructor concept map similarity does not correlate with examination performance. Research outcomes are discussed concerning possible sources of variation in student and faculty knowledge structures.
Helping undergraduates repair faulty mental models in the student laboratory.
Authors: Modell H I , Michael J A , Adamson T , Goldberg J , Horwitz B A , Bruce D S , Hudson M L , Whitescarver S A , Williams S
Published: December 2017

Over half of the undergraduate students entering physiology hold a misconception concerning how breathing pattern changes when minute ventilation increases. Repair of this misconception was used as a measure to compare the impact of three student laboratory protocols on learning by 696 undergraduate students at 5 institutions. Students were tested for the presence of the misconception before and after performing a laboratory activity in which they measured the effect of exercise on tidal volume and breathing frequency. The first protocol followed a traditional written "observe and record" ("cookbook") format. In the second treatment group, a written protocol asked students to complete a prediction table before running the experiment ("predictor" protocol). Students in the third treatment group were given the written "predictor" protocol but were also required to verbalize their predictions before running the experiment ("instructor intervention" protocol). In each of the three groups, the number of students whose performance improved on the posttest was greater than the number of students who performed less well on the posttest (P < 0.001). Thus the laboratory protocols helped students correct the misconception. However, the remediation rate for students in the "instructor intervention" group was more than twice that observed for the other treatment groups (P < 0.001). The results indicate that laboratory instruction is more effective when students verbalize predictions from their mental models than when they only "discover" the outcome of the experiment.
Peer instruction improves performance on quizzes.
Authors: Rao S P , DiCarlo S E
Published: December 2017

Peer instruction is a cooperative-learning technique that promotes critical thinking, problem solving, and decision-making skills. Benson's think-pair-share and Mazur's peer-instruction techniques are simple cooperative exercises that promote student's participation in class and increase student's interaction with each other and with the instructor in a large classroom. We borrowed concepts from Benson and Mazur and applied these concepts to enhance student involvement during the respiratory component of the medical physiology class. The medical physiology class consisted of 256 first-year medical students. The peer-instruction technique was used for 10 classes. Each class of 50 min was divided into three or four short presentations of 12-20 min. Each presentation was followed by a one-question, multiple-choice quiz on the subject discussed. Questions ranged from simple recall to those testing complex intellectual activities. Students were given 1 min to think and to record their first answer. Subsequently, students were allowed 1 min to discuss their answers with their classmates and possibly correct their first response. The percentage of correct answers increased significantly (P < 0.05) after discussion for both recall and intellectual questions. These data demonstrate that pausing three to four times during a 50-min class to allow discussion of concepts enhanced the students level of understanding and ability to synthesize and integrate material.
PULMONARY AND RENAL PRESSURE-FLOW RELATIONSHIPS: WHAT SHOULD BE TAUGHT?
Authors: Goodman Barbara E.
Published: December 2017

This article is from a symposium presented at the annual meeting of the Human Anatomy and Physiology Society (HAPS) on June 11, 2000. The presentation was funded under the auspices of a National Science Foundation Course, Curriculum, and Laboratory Improvement Program entitled “Development of Active Learning Materials for Physiology and Functional Anatomy: A Cooperative HAPS-APS Initiative.” This symposium was part of the first module to be developed on “gradients and conductances: what flows where and why?” This presentation was designed to model the usefulness of the general model of gradients and conductances in the physiology and pathophysiology of the respiratory and renal systems. Thirteen different examples of pressure-flow-resistance and concentration-flux relationships are introduced; several ideas for active-learning activities and simple figures appropriate for undergraduate physiology classes are included. The symposium assumes that undergraduate students have already learned about diffusion, osmosis, and the basic principles of cardiovascular physiology. The presentation was designed to follow a symposium entitled: “Cardiovascular pressure-flow relationships: what should be taught?”
Effects of 3'-deoxycytidine on rRNA synthesis in toad bladder: analysis of response to aldosterone
Authors: Rossier B. C. , Wilce P. A. , Inciardi J. F. , Yoshimura F. K. , Edelman I. S.
Published: December 2017

Previous studies showed that aldosterone augments transepithelial active Na+ transport and the incorporation of [3H]uridine into polyadenylated RNA (poly(A)(+)-RNA) (putatively mRNA) early in the latent period. Soon thereafter, incorporation of [methyl-14C] groups, as well as [3H]uridine into rRNA is also increased. To evaluate the role of rRNA in mineralocorticoid action, the inhibitor 3'-deoxycytidine was used in studies on the urinary bladder of the toad Bufo marinus. 3'-deoxycytidine suppressed the incorporation of [methyl-14C] and [3H]uridine into nuclear precursors of rRNA and subunits of cytoplasmic rRNA. In contrast, 3'-deoxycytidine inhibited incorporation of ]3H]uridine into cytoplasmic poly(A)(+)-RNA minimally. In control experiments, 3'-deoxycytidine had no significant effect on Na+ transport, measured as the short-circuit current (scc), when given alone. 3'-Deoxycytidine also had no significant effect on the aldosterone-dependent increase in scc. In the presence of 3'-deoxycytidine, aldosterone enhanced both the scc and the incorporation of [3H]uridine into poly(A)(+)-RNA significantly. We conclude that during the first 3 h, the mineralocorticoid action of aldosterone is not sensitive to inhibition of rRNA synthesis. Previous studies, however, implicate mRNA synthesis in this early response.
Contractile properties of rat soleus muscle: effects of training and fatique
Authors: Fitts R. H. , Holloszy J. O.
Published: December 2017

The effects of exercise training and fatique on the contractile properties of rat soleus muscles have been investigated. Prolonged exercise, consisting of 2 h or daily treadmill running, induced small but significant decrease in contraction time, one-half relaxation time, and maximum tetanic tension (Po), and increase in the peak rate of tension development (dP/dt) during a twitch, and an increase in maximum shortening velocity (Vmax). The 20% increase in Vmax was proportional to the previously reported increase in actomyosin ATPase induced by 2 h of daily running. These results indicate that prolonged training can induce modifications of the neurally determined contractile properties of skeletal muscle. To investigate the effects of fatigue, soleus muscles were stimulated in situ with 250-ms trains of 100 Hz at a rate of 110 trains per minute for 30 min. This resulted in a 32% decrease in Po, a 48% decline in peak tetanic dP/dt, and a 12% decrease in Vmax in muscles of untrained animals. Muscles that had adapted to exercise were significantly protected against the decrease in Po (only an 8% decrease) and Vmax (no significant decrease) but not against the decline in peak dP/dt.
Estimates of quantal-release and binomial statistical-release parameters at rat neuromuscular junction
Authors: Wilson D. F.
Published: December 2017

Quantal-release and binomial statistical-release parameters were examined in the isolated rat diaphragm phrenic nerve preparation. The muscle resting potentials were reduced by cutting the muscle fibers to prevent muscle action potentials and contractions. The cutting technique was modified to allow persistent observation of miniature end-plate potentials (MEPPs) and end-plate potentials (EPPs) with intracellular recording techniques. Direct estimates of quantal release were examined and compared with predicted binomial and Poisson distributions. The results indicate that release is binomial when the nerve is stimulated with low- or high-frequency stimuli. The indirect method of estimating quantal release (variance method), which assumes release is described by a Poisson distribution, seriously overestimates quantal release. The binomial analysis indicates that the statistical store is small (less than 90 quanta) and that most of these quanta are released with each nerve impulse.
Intracellular pH transients in rat diaphragm muscle measured with DMO
Authors: Roos A. , Boron W. F.
Published: December 2017

Changes of the intracellular pH of rat diaphragm muscle were monitored at 30-min intervals with the weak acid DMO (5,5-dimethyl-2,4-oxazolidinedione). Transferring the muscle from a CO2-containing to a CO2-free solution caused intracellular pH (pHi) to rise by an average of 0.18 during the first 30 min and then to level off at a slightly lower value over the next 60-90 min. Transferring the muscle from a CO2-free to a CO2-containing solution caused pHi to fall by 0.18 during the first 30 min and then to recover by 0.05 over the next 90 min. Subsequent return to the CO2-free solution caused pHi to overshoot the control value by 0.10. Both the recovery and the overshoot can be accounted for by an acid-extruding pump. Intracellular acid loading with 118 mM DMO similarly caused pHi to fall initially, to recover slowly during the acid loading, and then to overshoot the control pHi on removal of the acid load. In the absence of HCO3-/CO2, acid extrusion was reduced by about a fifth. SITS (4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid) had no effect. The absence of either Na+ or Cl- from HCO3-/CO2- free solution reduced acid extrusion by about a half.
Electric current generated by squid giant axon sodium pump: external K and internal ADP effects
Authors: Abercrombie R. F. , de Weer P.
Published: December 2017

The operation of the sodium pump of giant axons of the squid, Loligo pealei, has been studied simultaneously in two independent ways: 1) by measuring sodium efflux with 22Na, and 2) by calculating the transmembrane current generated by the pump from measurements of membrane resistance and digitalis-sensitive membrane potential. In normal, untreated axons, the effect of increasing the external potassium concentration on both sodium efflux and pump current is similar, which suggests that Na:K pump stoichiometry remains relatively constant in the range of 0-20 mM external K. The data are compatible with a 3:2 Na:K ratio. In axons whose intracellular ADP level has been elevated by injection of L-arginine, a large, electrically silent, cardiotonic steroid-sensitive sodium efflux takes place in the absence of external potassium; this suggests that pump-mediated Na:Na exchange is 1:1 or electroneutral. Finally, elevation of external potassium levels causes the appearance, in high-ADP axons, of electrogenic pumping, with little effect on sodium efflux; hence, in contrast to what is seen in normal (low-ADP) axons, the charge translocated, per sodium ion extruded, increases sharply with increasing extracellular potassium levels.
Mechanism of membrane stabilization by calcium in vascular smooth muscle
Authors: Webb R. C. , Bohr D. F.
Published: December 2017

In this study we observed relaxation in helical strips of rat tail artery in response to high concentrations of calcium after contraction induced by 10(-7) g/ml norepinephrine. This action of calcium on vascular smooth muscle contraction is referred to as the “membrane-stabilizing effect” of calcium. The current study demonstrates that changes caused by many of the variables that alter this relaxation induced by calcium parallel changes in relaxation in response to potassium; both are attenuated by ouabain, low sodium, reduced temperature, and low potassium. Relaxation produced by manganese is not similarly affected. Because potassium has been shown to cause relaxation of vascular smooth muscle by increasing the activity of sodium-potassium ATPase, we conclude that the relaxation produced by high concentrations of calcium is dependent on the activity of sodium-potassium ATPase; that produced by manganese is not.
Influence of pH on elastic deformability of the human erythrocyte membrane
Authors: Crandall E. D. , Critz A. M. , Osher A. S. , Keljo D. J. , Forster R. E.
Published: December 2017

Fresh human blood was diluted 1:5000 in buffered saline-sucrose solution and titrated to a pH varying from 4.5 to 10.5 with 0.1 N HCl or 0.1 N NaOH. Circular regions of the membrane of individual cells were then deformed at 25 degrees C by aspiration into a micropipette having an internal tip diameter of 0.9–1.4 micron. A membrane surface elasticity modulus, mu (dyn/cm), was computed from the relationship between length of the aspirated membrane and the deforming pressure according to a two-dimensional membrane model. Surface elasticity increases with decreasing pH and with time after the cell suspension is acidified, rising several orders of magnitude with a t1/2 of 1--5 h as pH is lowered from 7.2 to 4.6. This increase in mu is only partially reversible. pH greater than 7.2 had little effect on mu. Membrane surface elasticity is not affected by variations in external [Ca2+] over the range of 0--50 mM, tonicity of the suspension medium from 275--400 mosM, or age of 0--50 h. Addition of 50 mM NaHCO3 to the medium increases the rate of change of mu at a given pH. These results suggest that the elastic properties of the red cell membrane are largely determined by interactions among structural proteins located on the cytoplasmic surface of the membrane and that these interactions are initiated by changes in intracellular pH.
Phosphorylation of a bovine cardiac actin complex
Authors: Bailin G.
Published: December 2017

A bovine cardiac actin-tropomyosin-troponin complex was phosphorylated in the presence of [gamma-32P]ATP, Mg2+, adenosine 3',5'-monophosphate (cyclic AMP), and bovine cardiac cyclic-AMP-dependent protein kinase. Approximately 81% of the [32P]phosphate incorporated was identified as phosphoserine and phosphothreonine. Gel electrophoresis studies showed that 55% of the [32P]phosphate was associated with the inhibitory component of troponin (Tn-I) and 24% with a protein resembling the tropomyosin-binding component of troponin in the actin complex, respectively. The phosphorylation of Tn-I in the actin complex was inhibited 30% when Ca2+ was increased from 0.1 to 50 muM, but phosphorylation of other components was not affected by increasing Ca2+ concentration. Half-maximal calcium activation of the ATPase activity of reconstituted actomyosins made with the [32P]phosphorylated cardiac actin complex and cardiac myosin was shifted to Ca2+ values higher than those of actomyosins made with the nonphosphorylated actin complex.
Cation exchange and glycoside binding in cultured rat heart cells
Authors: McCall D.
Published: December 2017

The Na/K-exchange characteristics, ouabain-binding kinetics, and Na pump turnover rates of synchronously contracting monolayers of neonatal rat myocardial cells were studied. The cells exchange Na rapidly (T1/2 = 35 s) with a mean Na flux of approximately 25 (pmol/cm2)/s. The half time (T1/2) of K exchange is much longer (12 min); the mean K flux is 13 (pmol/cm2)/s. Active Na/K transport, as measured by K influx, is relatively ouabain sensitive, and 10(-6) M ouabain produces half-maximal inhibition. Ouabain (10(-2)M) inhibits 60% of the Na efflux and 75% of the K influx. The cells bind [3H]ouabain rapidly (T1/2 = 8 min), but release it very slowly (T1/2 = 11 h), and both the amount bound and the rate of binding were inversely proportional to extracellular K. Specific [3H]ouabain binding demonstrates saturation reaching a maximum of 1.6 x 10(6) molecules per cell at 2 x 10(-7) M [3H]ouabain. From cell surface area and ouabain-sensitive flux measurements, the Na pump density was calculated at 720/micrometer2 with an individual pump turnover rate of 50/s. Thus the studies indicate that despite their neonatal origin, the behavior of the Na pump in these cells is very similar to that in other mammalian tissues.
Hexose transport and phosphorylation by capillaries isolated from rat brain
Authors: Betz A. L. , Csejtey J. , Goldstein G. W.
Published: December 2017

Hexose transport and phosphorylation were studied in capillary segments isolated from rat brain. Uptake of 3-O-methyl-D-glucose (3MG) could be inhibited by cytochalasin B, phloretin, and phlorizin, but not by 2,4-dinitrophenol or ouabain. 2-Deoxy-D-glucose (2DG), D-glucose, galactose, and mannose inhibited 3MG uptake, while L-glucose, fructose, and ribose did not. Accelerative exchange diffusion of 3MG was demonstrated. At equilibrium, the intracellular concentration of hexose did not exceed the external concentration, and transport was, therefore, equilibrative rather than accumulative. Transport of 2DG and D-glucose was not rate limiting for metabolism. When incubated in 5 mM D-glucose, the endothelial cells contained a large pool of free glucose. L-Glucose entered capillaries more slowly than other hexoses and served as a marker for simple diffusion of sugars into the cells. Our results suggest that sugar uptake into isolated brain capillaries occurs by a transport system similar to the one responsible for glucose transport across the blood-brain barrier in vivo.
Effects of serum on membrane transport. III. Serum and inhibition of lysine transport
Authors: Strauss P. R.
Published: December 2017

Rabbit lung macrophages have been shown to transport lysine by means of a single carrier-mediated system that is depressed after relatively short incubations with 1% normal rabbit serum (NRS). Our present results show that three amino acids, glutamine, phenylalanine and tyrosine, at or near the concentration found in 1% NRS, are involved intracellularly in regulating lysine influx across the plasma membrane. The means by which they do so requires a 20- to 30-min preincubation, the effect is maintained for 45 min in their absence, and both maximal velocity and affinity of lysine for its carrier are altered in an apparently uncompetitive fashion. The kinetic data are unlike those reported for other trans phenomena involved in amino acid transport. We propose that the effect of internal inhibitor on lysine influx probably does not involve the direct interaction of the transamino acid on the lysine carrier.
Thyroxine and Na+ transport in toad: role in transition from poikilo- to homeothermy
Authors: Rossier B. C. , Rossier M. , Lo C. S.
Published: December 2017

The effects of thyroxine (T4) on Na+ transport, oxygen consumption (QO2), and Na+-K+-ATPase activity were studied in the urinary bladder and liver of the toad Bufo marinus. In the bladder, T4 in vitro (10(-8) to 10(-6) M) had no significant effect on these parameters during 15 h of incubation. When injected intraperitoneally (approximately 20 microgram/(kg body wt.day) for 6 days), T4 lowered base-line, short-circuit current by 62% (P less than 0.0025) and potential difference by 37% (P less than 0.001), increasing tissue resistance by 40% (P less than 0.02). T4 depressed QO2/DNA (-25%, P less than 0.05) with no significant effect on Na+-K+-ATPase activity. In liver, T4 increased the recovery per cell DNA of mitochondrial proteins by 32% (P less than 0.025), corresponding to an increased QO2 (stage IV) of isolated mitochondria per cell DNA (+54%, P less than 0.01). There was no significant effect on Na+-K+-ATPase activity. These results suggest that, unlike its function in the rat, T4 in the toad does not regulate cellular thermogenesis by inducing Na+-K+-ATPase. This major difference could account at least in part for the transition from poikilothermy to homeothermy. In addition, T4 has a distinct inhibitory effect on Na+ transport in the urinary bladder, which suggests an antagonism to the action of aldosterone.
Correlated release of acetylcholine and protein from the neuromuscular junction
Authors: Musick J. R.
Published: December 2017

Transmitter release at adrenergic synapses is accompanied by release of chromogranin proteins, which are contained in synaptic vesicles. To determine if a similar phenomenon occurs at the neuromuscular junction, correlated release of acetylcholine (ACh) and protein was investigated using in vitro neuromuscular preparations (phrenic nerve-diaphragm muscle of the rat and mouse, sciatic nerve-sartorius muscle of Rana pipiens and R. catesbeiana). Nerve stimulation of curare-paralyzed preparations increased the rate of efflux of Lowry-reactive material relative to control values. Stimulus-specific responses outlasted the period of neural stimulation. Stimulus-induced release of Lowry-reactive material was correlated with ACh release since it was Ca2+ dependent and Mg2+ antagonized. Conditions that potentiate spontaneous ACh release also significantly increased the rate of efflux of Lowry-reactive material. Most of the Lowry-reactive material released with ACh is not a secretory product of synaptic vesicles because the amount released exceeds the contents of synaptic vesicles that undergo exocytosis. It is concluded that ACh release from the neuromuscular junction is accompanied by release of proteinaceous material that is not entirely derived from synaptic vesicles.
Mechanism of insulin action on resting membrane potential of frog skeletal muscle
Authors: Moore R. D. , Rabovsky J. L.
Published: December 2017

At a concentration that stimulates the Na pump, insulin hyperpolarizes the plasma membrane of frog sartorius in the presence of substrate-free Ringer. The hyperpolarization ranged from 3.5 to 7.3 mV and averaged 4.7 mV. Ouabain, 10(-4) M, completely blocked the effect of insulin on the membrane potential. Moreover, ouabain completely reversed the insulin-induced hyperpolarization within 20 min. The hyperpolarization produced by insulin was not associated with a detectable increase in the ratio of K+ permeability to Na+ permeability nor with a detectable increase in the concentration of intracellular K+, although a depletion of K+ near the external surface of the membrane cannot be excluded. The results clearly indicate that the hyperpolarization is secondary to stimulation of the Na pump by insulin.
Active and passive Ca movements in dog red blood cells and resealed ghosts
Authors: Parker J. C.
Published: December 2017

Dog red blood cells accumulate Ca rapidly when deprived of substrate or cooled to 5 degrees C. The latter effect is reversible as the cells are rewarmed to body temperature. Resealed ghosts extrude Ca, provided ATP is incorporated in them. Passive fluxes of Ca are stimulated by Na on the opposite side of the membrane, consistent with a model for Ca-Na countertransport. Quinidine, cell shrinkage, and low pH--all known to suppress net Ca influx--have no accelerating effect on Ca efflux, thus validating earlier conclusions about the variability of the coupling ratio for Ca-Na exchange. The significance of these findings for cell volume regulation is discussed.
Membrane potentials and sugar transport by ATP-depleted intestinal cells: effect of anion gradients
Authors: Carter-Su Christin , Kimmich George A.
Published: December 2017

Rotenone or dinitrophenol treatment was used to decrease cellular ATP levels in isolated chicken intestinal epithelial cells by over 90% and to produce a cell population in which no steady-state accumulation of 3-O-methylglucose (3-OMG) against a concentration gradient is observed. In the presence of imposed inward-directed Na-anion gradients, these cells accumulate 3-OMG against a concentration gradient. The degree of maximal 3-OMG accumulation and initial influx stimulation in the presence of a given anion or combined Na-anion gradient can be correlated with the magnitude of the diffusion potential as determined by the membrane permeability of the given anion (SCN- > Cl- > isethionate- > SO42-). 3-OMG influx in the presence of a large NaCl gradient is comparable in ATP-depleted and normally energized cells. The slight difference in influx (energized > ATP depleted) is diminished by ouabain, suggesting that energized cells maintain a larger membrane potential (diffusion potential or rheogenic Na+-K+-ATPase ion pump-generated potential) than the ATP-depleted cells. Although initial rates of 3-OMG uptake into Na+-depleted normally energized cells also varies with the anion gradient, these differences disappear with time of incubation in Na+ or when cells are preincubated in Na+. In this situation, function of a rheogenic Na+ pump can establish a membrane potential in contrast to the case with ATP-depleted cells, which have a potential only as long as imposed ion gradients are maintained. All these experiments point to an important role for the electrical membrane potential as a driving force for Na+-dependent solute transport systems in both ATP-depleted and normally energized cells.
Suppression of myotonia in dystrophic chicken muscle by phenytoin
Authors: Entrikin R. K. , Bryant S. H.
Published: December 2017

We describe myotonic electromyographic activity in muscles of genetically dystrophic chickens and show that this activity is antagonized in vivo by doses of phenytoin (DPH) that improve righting ability. To test the possibility that the in vivo effects of DPH can be accounted for by a direct action on skeletal muscle we studied posterior latissimus dorsi fibers in vitro at 23 degrees C with intracellular microelectrodes. Compared to normal fibers, fibers from untreated dystrophic chicks had larger diameters, increased membrane capacitance, longer latencies at rheobase, and a greater tendency to fire repetitively in response to direct stimulation. DPH (10 or 50 micrograms/ml in the bath solution) decreased latencies at rheobase and repetitive firing in fibers from untreated chicks. In DPH-free solution fibers from dystrophic chicks treated chronically with DPH were still abnormal with respect to latencies at rheobase and ease of repetitive firing. The data support the hypothesis that abnormalities of membrane electrical properties are major features of dystrophic chicken muscles and furthermore, show that DPH suppresses, but does not abolish, these abnormalities.
Membrane permeability during low potassium depolarization in sheep cardiac Purkinje fibers
Authors: Lee C. O. , Fozzard H. A.
Published: December 2017

Exposure of sheep Purkinje fibers to low [K]o leads to marked depolarization to a stable potential of about -40 mV. This level is equivalent to the plateau of the Purkinje fiber action potential. The low [K]o depolarization could be prevented by removal of [Na]o and was modified by tetrodotoxin. The membrane potential in the depolarized state was unresponsive to changes in [Cl]o or [Ca]o and it was poorly responsive to changes in [K]o between 0 and 2 mM. Repolarization was induced by decrease in [Na]o with a slope response of 30 mV/10-fold change in [Na]o. Average internal K activity (aK) in the resting state with a [K]o of 5 mM was 121.4 mM for a membrane potential of -80 mV. During low K depolarization aK was 119.7 mM with a membrane potential of -34 mV. The depolarization was therefore due to a change in membrane permeability, with little change in aK. Upon restoration of [K]o the fiber repolarized to values transiently more negative than the prior resting potential. These transient potentials were more negative than the K equilibrium potential (VK), if it is calculated assuming a uniform [K]o. The hyperpolarization was reduced by ouabain [10(-6)] or by low [Ca]o.
Mechanical properties and functions of the myoepithelium in the eccrine sweat gland
Authors: Sato K. , Nishiyama A. , Kobayashi M.
Published: December 2017

Contractile properties of an isolated segment of the secretory coil of the monkey palm eccrine sweat gland were studied in vitro with a transducer. Contraction of up to 10 mgf was induced with acetylcholine but not with alpha or beta adrenergic agonists, caffeine, prostaglandin E1, or by a calcium ionophore A23187. Other features included K+ contracture, staircase effect, poor extensibility, length-tension relationship with a peak tensile response at 115--120% of the resting length, and requirement of Ca2+. The function of myoepithelium is unlikely to expulse the preformed sweat because the amount of preformed sweat is small, K+-contracture failed to expulse sweat, and because myoepithelial contraction was not induced by such stimulants of sweat secretion as A23187, phenylephrine, isoproterenol, and prostaglandin E1. The maximal transverse tension of 20 mgf during acetylcholine stimulation under resting tension was calculated to support the luminal hydrostatic pressure of approximately 500 mmHg. Thus the function of the myoepithelium may be to render structural support for the secretory epithelium.
Possible role of cyclic GMP in stimulus-secretion coupling by salt gland of the duck
Authors: Stewart D. J. , Sax J. , Funk R. , Sen A. K.
Published: December 2017

Stimulation of salt galnd secretion in domestic ducks in vivo increased the cyclic GMP concentration of the tissue, but had no effect on cyclic AMP levels. Methacholine, which is known to stimulate sodium transport by the glands both in vivo and in vitro, stimulated ouabain-sensitive respiration in salt gland slices. Cyclic GMP stimulated ouabain-sensitive respiration to the same extent as methacholine. Guanylate cyclase stimulators, hydroxylamine and sodium azide, also stimulated ouabain-sensitive respiration. The stimulation of ouabain-sensitive respiration by methacholine was blocked either by atropine or by removal of calcium from the incubation medium. The stimulation of ouabain-sensitive respiration by cyclic GMP still occurred in the absence of calcium. The above observations seem to indicate that cyclic GMP acts as a tertiary link in the process of stimulus-secretion coupling in the tissue.
Contractile, biochemical, and histochemical properties of thyrotoxic rat soleus muscle
Authors: Fitts R. H. , Winder W. W. , Brooke M. H. , Kaiser K. K. , Holloszy J. O.
Published: December 2017

The effects of thyrotoxicosis on the contractile properties of soleus muscle were examined in rats given 3 mg of T4 and 1 mg of T3 per kg of diet for 6–8 wk. Thyrotoxicosis induced significant decreases in isometric twitch contraction time (CT), one-half relaxation time, and peak twitch tension. The Ca2+ uptake activity of the sarcoplasmic reticulum (SR) was increased in the thyrotoxic muscles; this adaptation in the SR provides a possible mechanism for the alterations in isometric contractile properties. Thyrotoxicosis induced a large increase in fibers classified as type 2, on the basis of an alkali-stable histochemical reaction for ATPase, in the soleus. Although this reaction is commonly interpreted as indicating that a muscle is fast, maximum shortening velocity (Vmax) and Mg2+ activated actomyosin ATPase activity were unaffected in the thyrotoxic soleus. Our findings provide evidence that CT and Vmax can vary independently and that the histochemical ATPase reaction may not always reflect the biochemical properties that make myosin fast or slow.

actomyosin ATPase; histochemical ATPase reaction; isometric contraction time; maximum shortening velocity; one-half relaxation time; sarcoplasmic reticulum; skeletal muscle

Submitted on April 13, 1979

Accepted on August 7, 1979
Structural and functional study of control of canine tracheal smooth muscle
Authors: Kannan M. S. , Daniel E. E.
Published: December 2017

The structural bases for myogenic and neurogenic control of canine tracheal smooth muscle were studied. At optimum lengths, strips of muscle showed insignificant neurogenic or myogenic tone. Atropine and/or tetrodotoxin blocked the contractile responses elicited on electrical field stimulation of intrinsic nerves. After raising the tone with tetraethylammonium ion and in the presence of atropine, field stimulation of nerves caused a relaxation, a major component of which was blocked by propranolol and/or tetrodotoxin, suggesting an effect mediated through interaction of mediator released from sympathetic nerves with beta-adrenergic receptors. Electron microscopic studies revealed gap junctions between extensions of smooth-muscle cells and a sparse innervation. The axonal varicosities, corresponding to cholinergic (predominantly) and adrenergic (occasionally) nerves, were seen predominantly in the clefts between cell bundles. The physiological responses were compared with the morphological features. Although this muscle exhibits multiunit behavior in vitro, implying that nerves initiate the coordinate activity, its ultrastructural features suggest a potential for single-unit behavior.
[3H]ouabain binding during the monolayer organization and cell cycle in MDCK cells
Authors: Rabito C. A. , Tchao R.
Published: December 2017

The specific binding of [3H]ouabain in an epithelial cell line derived from a dog kidney (MDCK) was determined during epithelial reorganization and also during the cell cycle. In suspended cells, the specific binding of [3H]ouabain is reduced 67% compared with the binding obtained in a complete monolayer. After plating back these cells on a permeable support, both transepithelial electrical resistance and [3H]ouabain binding increase with time of incubation. [3H]ouabain binding decreases during S and G2 phases of the cell cycle to reach a minimum during mitosis and increases again during GI. The transepithelial electrical resistance, determined simultaneously, shows the same behavior. The reduction in the number of [3H]ouabain binding sites in two different circumstances in which the epithelial membrane organization is disrupted and the increase in [3H]ouabain binding sites when the epithelial membrane is reorganized are consistent with the hypothesis that the number of pumping sites responsible for the active step in the transepithelial active transport is additional to the number required to maintain the intracellular ionic composition.
Effect of temperature on mechanical and myothermic properties of rabbit smooth muscle
Authors: Gibbs C. L. , Loiselle D. S.
Published: December 2017

The mechanical performance and the heat production of 18 rabbit rectococcygeus muscles have been measured at 19 degrees C and 29 degrees C. The rate of energy liberation in a tetanus was 2.96 +/- 0.14 mW/g at 19 degrees C and 5.84 +/- 0.25 mW/g at 29 degrees C. At both temperatures there was a linear relationship between total (initial + recovery) heat production and the stress-time integral for stimulus durations up to 13 s. The slope of the relationship had a Q10 of 1.8. Recovery heat evolution, measured after mechanical relaxation was complete, was approximately exponential in character. The final time constant for recovery heat liberation was 63.1 +/- 5.5 s at 19 degrees C and 32.3 +/- 2.4 s at 29 degrees C. After-loaded isotonic force-velocity data were fitted with the hyperbolic version of Hill's characteristic equation (A. V. Hill. Trails and Trials in Physiology. London: Arnold, 1965). The a/Po ratio was practically temperature independent, but maximal shortening velocity and the constant b had Q10's of 2.5 and 2.7, respectively.
Nonrandom distribution of gap junctions between pancreatic beta-cells
Authors: Meda P. , Denef J. F. , Perrelet A. , Orci L.
Published: December 2017

The numerical and spatial distribution of gap junctions between insulin-containing cells (beta-cells) under resting and stimulated conditions of insulin secretion were quantitatively analyzed in freeze-fracture replicas of isolated rat islets of Langerhans. The results show that the beta-cells located at the periphery of the islet have twice as many gap junctions per unit membrane area as the beta-cells situated in the islet center. In both locations, gap junctions assumed a nonrandom clustering on the beta-cell membranes. During stimulation of insulin secretion, the gap junctions were found increased between the central and between the peripheral beta-cells. The degree of their clustering was also modified. The latter change depended both on the location of the gap junctions in the islet and on the type of stimulation used (high glucose or glibenclamide).
Effect of membrane potential on Na+-dependent sugar transport by ATP-depleted intestinal cells
Authors: Carter-Su C. , Kimmich G. A.
Published: December 2017

The role of the membrane potential as a component of the thermodynamic driving force and as a determinant of kinetic parameters of Na+-dependent sugar transport was investigated using ATP-depleted isolated chicken intestinal cells. Inside-negative membrane potentials were established by incubating K+-loaded rotenone-inhibited cells with valinomycin in a low K+ medium. Overshoots of 3-O-methylglucose (3-OMG) accumulation as high as 10-fold were observed in the presence of valinomycin even in the absence of a Na+ chemical gradient. The magnitude of overshoot was diminished by decreasing the magnitude of the imposed K+ gradient and abolished altogether when nigericin was also included. An Eadie-Hofstee plot of initial flux data showed that the imposed membrane potential increases the Vmax of transport in the absence of a chemical gradient for Na+ from 3 to 12 nmol 3-OMG . mg protein-1 . min-1. The KT is not significantly altered. Similar kinetic results were obtained when a membrane potential as well as a Na+ gradient were imposed. These results suggest that the membrane potential is a more important contributor to alterations in the kinetics of transport than the Na+ chemical potential.
Regulation of Na+-dependent sugar transport in intestinal epithelial cells by exogenous ATP
Authors: Kimmich G. , Randles J.
Published: December 2017

Exogenous ATP (1 mM) exerts a dramatic biphasic effect on the accumulation of 100 micro M 3-O-methylglucose by isolated intestinal epithelial cells. The initial effect ensues approximately 15 s after exposure and inhibits 80% of the undirectional sugar influx. Cellular phosphatases totally degrade the added ATP within a period of 20 min leading to a reactivation of transport capability. The cells exposed to ATP ultimately establish a concentration gradient of sugar about twice that observed for control cells. Pyrophosphate (10 mM) delays the degradation of added ATP and prolongs the interval of transport inhibition. The late effect of gradient enhancement is still observed. No other nucleoside triphosphate induces the early inhibition of transport, but ADP is approximately two-thirds as effective as ATP. AMP and other molecules containing the adenine ring system can cause the late effect of gradient enhancement without causing an early transport inhibition. Because rotenone-treated ATP-depleted cells also show an ATP-induced inhibition of sugar influx, it seems likely that the early effect represents a direct modification of carrier capability rather than an effect mediated via an alteration of cellular energetics.