bluuebunny/crossref_metadata_2025 huggingface dataset:
Calcium‐activated potassium channels in rat muscle inactivate from a short‐duration open state.
Authors: Pallotta B S
Published: December 2014

Single channel recording techniques were applied to the study of activation and inactivation of Ca2+‐activated K+ channels in excised patches of membrane from rat muscle grown in culture. The concentration of intracellular surface Ca2+ was 0.6 microM in all experiments. The time course of the averaged open probability during depolarizing voltage steps of 1 s duration was biphasic for steps more positive than 20 mV; a rapid activation phase was followed by a much slower apparent inactivation with a single exponential time constant in the range of 400‐800 ms. The peak open probability and degree of inactivation increased as the steps were made more positive (+30 to +80 mV) or the holding potential more negative (+30 to ‐40 mV). A conditional probability analysis of the open intervals immediately adjacent to the long‐duration shut intervals resulting from inactivation revealed that transitions to and from the inactivated state occurred almost exclusively via a short‐duration open state (mean lifetime less than 200 microseconds). The rate of transition from the short‐duration open state to the inactivated state was rapid (typical rate constant 1879/s) and was sufficiently probable that as many as one out of every three short‐duration openings were followed by inactivation. Normal (non‐inactivating) closure of the channel from this open state was also rapid (rate constant 4003/s). At constant voltage (+50 mV) and Ca2+ (0.6 microM), the channel opened to the short‐duration open state approximately every 75 ms, suggesting that the slow inactivation of the averaged open probability might have been limited in part by the rate at which the channel entered the short‐duration open state.
Hypoxia releases a vasoconstrictor substance from the canine vascular endothelium.
Authors: Rubanyi G M , Vanhoutte P M
Published: December 2014

Experiments were designed to determine the role of the endothelium in the facilitation by anoxia of contractile responses of isolated coronary arteries. Rings and strips of canine coronary arteries, with or without endothelium, were suspended for isometric tension recording in modified Krebs‐Ringer bicarbonate solution. To determine the release of a vasoactive substance(s) from the endothelial cells, strips without endothelium were layered with strips containing endothelium. In rings and in layered preparations with endothelium, anoxia (95% N2‐5% CO2) augmented contractile responses to prostaglandin F2 alpha. Hypoxia (10 or 5% O2) caused contractions in the presence of indomethacin. Removal of the endothelium abolished the anoxic facilitation, and the hypoxic contractions. Inhibitors of cyclo‐oxygenase, lipoxygenase or phospholipase A2 or of adrenergic, serotonergic and histaminergic receptors did not prevent the response to anoxia. Likewise, inhibitors of the endothelium‐derived factor(s) (quinacrine, phenidone and methylene blue) did not affect the anoxic facilitation. Hypoxia and anoxia caused contraction of coronary arteries without endothelium when layered with femoral arteries and veins with endothelium. Anoxic facilitation was observed in femoral arteries, but not in femoral veins, with endothelium. These experiments indicate that hypoxia and anoxia cause the release of a diffusible vasoconstrictor substance(s) from endothelial cells. The sensitivity of smooth muscle of different anatomical origin to the facilitatory mediator(s) varies.
Flow through the foramen ovale of the fetal and new‐born lamb.
Authors: Anderson D F , Faber J J , Morton M J , Parks C M , Pinson C W , Thornburg K L
Published: December 2014

Right and left atrial pressures were measured in eight chronically instrumented fetal and neonatal lambs. Flows were measured with a combination of electromagnetic flow sensor and microsphere techniques. Three of the fetuses were ventilated in utero during the measurements. Four fetuses were studied as neonates immediately after spontaneous term delivery and one was studied as a normal fetus in utero. Data from these preparations were augmented with seven sets of previously reported data from normal fetuses in utero for analysis. Linear least‐squares regression analysis demonstrated that inferior caval vein flow into the right atrium was inversely related to right atrial pressure. This flow could not be demonstrated to depend on the velocity of blood in the inferior caval vein. Non‐linear least‐squares regression analysis of foramen ovale flow as a function of a power of the flow in the inferior caval vein revealed that the square of the velocity of blood in the inferior caval vein predicted foramen ovale flow. Of the two forces that determine foramen ovale flow in the fetus, pressure difference and kinetic energy, the latter was far larger than the former. These results support the theory that the fetal foramen ovale is maintained in an open position by the kinetic energy of the blood in the inferior caval vein.
Change in intracellular calcium ion concentration induced by caffeine and rapid cooling in frog skeletal muscle fibres.
Authors: Konishi M , Kurihara S , Sakai T
Published: December 2014

In a single skeletal muscle fibre treated with concentrations of caffeine below threshold for caffeine contracture, rapid lowering of the temperature of the bathing solution from 18 degrees C to below 5 degrees C induced a contracture (rapid cooling contracture). Intracellular Ca2+ concentration ([Ca2+]i) was recorded during rapid cooling contracture using aequorin. Low concentrations of caffeine often caused a slight elevation of the light signal in resting muscle without detectable tension. During rapid cooling contracture, the change in light signal occurred in three phases. The first phase was a transient change of [Ca2+]i accompanying slight tension. During the second phase, the light signal slowly increased as cooling produced maximum tension development. The third phase was an additional light signal induced after the second phase, even though the tension was saturated. The second and third phases were more sensitive to low concentrations of procaine (0.2‐0.5 mM) than the first phase. Synchronous oscillations of light and tension were often observed during the second phase. The light signal during rapid cooling contracture was only slightly affected by long incubation in Ca‐free or Ca‐rich solutions. These results are interpreted as follows. A low concentration of caffeine elevates cytoplasmic resting Ca2+ level without tension development. The oscillations of light and tension often observed in the second phase might represent a cyclic release of Ca2+ from the sarcoplasmic reticulum (s.r.). The third phase is considered to be due to a massive Ca2+ release by a Ca‐induced Ca‐release mechanism which might be similar to that in skinned fibres. The second phase is probably essential for generation of rapid cooling contracture tension and the third phase represents an excess Ca2+ for tension development.
Differences in maximum velocity of shortening along single muscle fibres of the frog.
Authors: Edman K A , Reggiani C , te Kronnie G
Published: December 2014

The velocity of 'unloaded' shortening (V0) and the force‐velocity relation were studied during fused tetani (0.5‐2.0 degrees C) in short successive segments along the entire length of single fibres isolated from the tibialis anterior muscle of Rana temporaria. The segments were defined by opaque markers of hair that were placed on the fibre surface, 0.5‐0.8 mm apart, from one tendon insertion to the other. The change in distance between two adjacent markers (one segment) was monitored by means of a photoelectric recording system, while the fibre was released to shorten isotonically between 2.2 and 2.0 micron sarcomere lengths. The accuracy of the V0 measurement was better than 4% in all parts of the fibre. V0 varied along the length of the fibre, each fibre having a unique velocity pattern that remained constant throughout the experiment. The difference between the highest and lowest values of V0 within the fibre varied between 11 and 45% of the fibre mean in thirty‐two preparations (mean difference 23 +/‐ 2%, S.E. of mean). An attempt was made to relate the V0 pattern to the fibre's orientation in the body in fourteen complete experiments. The highest values of V0 were obtained near the proximal end of the fibre, and there was a clear trend for V0 to assume lower values towards the distal end. The V0 pattern along the fibre did not correlate with the segments' capacities to produce force nor with the passive viscoelastic properties of the segments. Force‐velocity data obtained from individual segments provided a good fit to Hill's (1938) hyperbolic equation at loads less than 80% of the measured tetanic force. The curvature of the force‐velocity relation, defined by alpha/P0 in Hill's equation (P0 being the isometric force calculated from the hyperbolic function) varied between 0.09 and 0.46 in sixteen segments of six different fibres. V0 was inversely related to alpha/P0 according to the following regression: V0 = 3.21 ‐ 3.22. (alpha/P0), correlation coefficient, 0.72; P less than 0.005. No clear correlation between V0 and alpha/P0 existed at the whole‐fibre level. The results support the view that the kinetic properties of the myofilament system differ from one region to another along the length of a muscle fibre.
Muscarinic and peptidergic excitation of bull‐frog sympathetic neurones.
Authors: Jones S W
Published: December 2014

The large B cells of bull‐frog sympathetic ganglia are well known to be depolarized by slow synaptic transmission, muscarinic agonists, analogues of luteinizing hormone‐releasing hormone (LHRH), and substance P. Voltage‐clamp analysis shows that these actions result from two underlying mechanisms: inhibition of the M‐current, a voltage‐dependent potassium current; and in some cells, an inward current associated with an increase in conductance. The additional inward current appears as a voltage‐insensitive change in the instantaneous conductance (i.e. apparent leak conductance). The additional inward current is typically slower in onset and offset than is M‐current inhibition. It is typically seen for higher concentrations and longer durations of agonist application. In many cells, only a decrease in M‐current can be demonstrated. Muscarine inhibits the M‐current with 50% inhibition (I50) at 0.7 microM. At least 86% of the M‐current is muscarine sensitive. At comparable concentrations, oxotremorine produces less M‐current inhibition than does muscarine. Some analogues of teleost LHRH (T‐LHRH) are more potent as M‐current inhibitors than T‐LHRH itself. Those peptides tend to act more slowly than T‐LHRH. Substance P shows variable potency for M‐current inhibition, with I50 s ranging from 2 nM to greater than 2 microM on different cells. The response to long applications of substance P desensitizes in some cells, which has not been observed for comparable applications of muscarinic or LHRH agonists. Other tachykinins (including substance K) inhibit the M‐current. C‐terminal fragments of substance P are ineffective, and M‐current inhibition by substance P is not blocked by [D‐Pro2,D‐Trp7,9]‐ or [D‐Arg1,D‐Pro2, D‐Trp7,9,Leu11] substance P. The slow muscarinic excitatory post‐synaptic potential (e.p.s.p.) produces a graded inhibition of up to 90% of the M‐current. Occasional cells show an additional inward current with an associated increase in conductance during the slow e.p.s.p. This effect is less marked than with exogenous muscarinic agonists. The late, slow e.p.s.p., which is produced by stimulation of high threshold C‐fibre inputs and is resistant to cholinergic antagonists, also involves M‐current inhibition. An additional inward current can be observed in some cells. M‐current inhibition (by agonists or slow synaptic potentials) increases the number of spikes produced by a given depolarizing current, often allowing maintained firing. This action is not mimicked by equivalent depolarization, and is still seen when the cell is manually clamped to the original resting potential.(ABSTRACT TRUNCATED AT 400 WORDS)
Maximal perfusion of skeletal muscle in man.
Authors: Andersen P , Saltin B
Published: December 2014

Five subjects exercised with the knee extensor of one limb at work loads ranging from 10 to 60 W. Measurements of pulmonary oxygen uptake, heart rate, leg blood flow, blood pressure and femoral arterial‐venous differences for oxygen and lactate were made between 5 and 10 min of the exercise. Flow in the femoral vein was measured using constant infusion of saline near 0 degrees C. Since a cuff was inflated just below the knee during the measurements and because the hamstrings were inactive, the measured flow represented primarily the perfusion of the knee extensors. Blood flow increased linearly with work load right up to an average value of 5.7 l min‐1. Mean arterial pressure was unchanged up to a work load of 30 W, but increased thereafter from 100 to 130 mmHg. The femoral arterial‐venous oxygen difference at maximum work averaged 14.6% (v/v), resulting in an oxygen uptake of 0.80 l min‐1. With a mean estimated weight of the knee extensors of 2.30 kg the perfusion of maximally exercising skeletal muscle of man is thus in the order of 2.5 l kg‐1 min‐1, and the oxygen uptake 0.35 l kg‐1 min‐1. Limitations in the methods used previously to determine flow and/or the characteristics of the exercise model used may explain why earlier studies in man have failed to demonstrate the high perfusion of muscle reported here. It is concluded that muscle blood flow is closely related to the oxygen demand of the exercising muscles. The hyperaemia at low work intensities is due to vasodilatation, and an elevated mean arterial blood pressure only contributes to the linear increase in flow at high work rates. The magnitude of perfusion observed during intense exercise indicates that the vascular bed of skeletal muscle is not a limiting factor for oxygen transport.
Regional differences in responsiveness to octopamine within a locust skeletal muscle.
Authors: Evans P D
Published: December 2014

Regional differences in the physiological and biochemical responses to octopamine have been investigated in the extensor tibiae muscle of the hind leg of the locust. Octopamine increases the rate of relaxation of twitch tension generated by the slow motoneurone by different amounts in different regions of the muscle. It also increases the amplitude of twitch tension by the same amount in different regions of the muscle. The relaxation rate of fast twitch tension is increased by the same amount in all regions of the muscle innervated by the fast motoneurone. Octopamine also increases cyclic AMP levels by different amounts in different regions of both the extensor muscle and its antagonistic muscle, the flexor tibiae. In both muscles the maximal responses are obtained in the regions of the muscles containing the highest proportions of slow and intermediate muscle fibres as characterized by their contractile and ultrastructural properties. The results are discussed in terms of their functional significance and compared with examples of differential responses of different muscle fibre types in other invertebrate and vertebrate skeletal muscles.
Actions on gamma‐motoneurones elicited by electrical stimulation of cutaneous afferent fibres in the hind limb of the cat.
Authors: Johansson H , Sojka P
Published: December 2014

The reflex actions elicited by graded electrical stimulation of hind‐limb cutaneous (sural, superficial peroneal and tibial) nerves were investigated with intra‐ and extracellular micro‐electrode recordings in gamma‐motoneurones projecting to hind‐limb muscles in twenty‐four cats anaesthetized with alpha‐chloralose. In total, reflex responses of 100 gamma‐motoneurones were analysed. 82 of the gamma‐cells were classified as dynamic (43) or static (39) using the method of mesencephalic stimulation (Appelberg, Hulliger, Johansson & Sojka, 1982). The general responsiveness (i.e. number of input nerves with effect/number of input nerves tested) of the whole sample of gamma‐cells to stimulation of skin nerves was extremely high (94.8%). All negative observations were encountered among static and non‐classified gamma‐cells. Generally, the stimulation strengths needed for evoking effects in the gamma‐cells were very low. A majority of the excitatory effects in the dynamic cells appeared with stimulation intensities below 1.5 threshold (T), while most static cells were excited with stimulation strengths between 1.5 and 2 T. Also a statistical comparison of the populations of stimulation strength thresholds for the excitatory effects revealed a significant difference (P less than 0.0009) between dynamic and static gamma‐cells. By contrast, the thresholds for inhibitory effects in dynamic cells were slightly higher than for excitatory effects (P less than 0.0009). As regards excitation of static cells, inhibition of dynamic cells and inhibition of static cells, no statistically significant threshold differences were found. A strong dominance of excitation over inhibition was found in both dynamic and static flexor (posterior biceps and semitendinosus) gamma‐motoneurones from all input nerves. In comparison to flexor gamma‐motoneurones, there was a much higher incidence of inhibitory and mixed (excitatory and inhibitory) responses in extensor (triceps) gamma‐motoneurones, from all nerves tested. For dynamic cells there was an about even balance between excitation and inhibition, while for static cells inhibition seemed to prevail. The latencies for excitatory effects in dynamic gamma‐cells differed from those in static gamma‐cells (P less than 0.027). The shortest latencies of excitatory effects found for dynamic gamma‐cells indicate a disynaptic coupling, while for static cells the shortest route seemed to involve at least three synapses.(ABSTRACT TRUNCATED AT 400 WORDS)
Potassium channels in cultured bovine adrenal chromaffin cells.
Authors: Marty A , Neher E
Published: December 2014

K channels of bovine adrenal chromaffin cells were studied using patch‐clamp techniques. Whole‐cell K currents measured near +10 mV were much larger in 1 mM‐external Ca than in Ca‐free saline. Noise analysis suggested that this Ca‐dependent current was carried by a large unitary conductance channel, called BK channel, which was previously described in inside‐out patches (Marty, 1981). The Ca‐dependent K current near +10 mV declined with time due to 'run‐down' of Ca channels. At the same time, a fraction of the outward current observed above +50 mV was also eliminated. This outward current component probably represents K efflux through Ca channels. Whole‐cell Ca‐dependent K currents were studied using various Ca buffers. EGTA buffers were surprisingly inefficient: in order to block the current entirely, it was necessary to use an isotonic EGTA solution and to increase internal pH. 1,2‐bis(o‐aminophenoxy)ethane‐N,N,N',N'‐tetraacetic acid (BAPTA) was at least five times more efficient than EGTA. In isolated patches three types of single‐channel K currents were observed. Under normal ionic conditions (140 mM‐K inside, 140 mM‐Na outside), the unitary conductances measured between ‐20 and +40 mV were 96 pS, 18 pS and 8 pS. The 96 pS channels are the Ca‐dependent BK channels. 18 pS and 8 pS channels were both activated and then inactivated by membrane depolarization. Both displayed complex kinetics; single‐channel currents were grouped in bursts. Activation and inactivation kinetics were faster for the 18 pS channel (therefore termed FK channel, for fast K channel) than for the 8 pS channel (SK channel, for slow or small amplitude channel). The voltage dependence of opening probability was steeper for the FK channel as compared to the SK channel.
Calcium entry into voltage‐clamped presynaptic terminals of squid.
Authors: Augustine G J , Charlton M P , Smith S J
Published: December 2014

Voltage‐clamp measurements of Ca current and Arsenazo III measurements of intracellular Ca concentration were used to assess Ca ion entry into voltage‐clamped presynaptic terminals of squid 'giant' synapses. Depolarization of voltage‐clamped terminals filled with Arsenazo III produced absorbance changes consistent with intracellular accumulation of Ca ions. These intracellular Ca transients had a bell‐shaped dependence on presynaptic potential and were maximal at approximately ‐10 mV. Arsenazo III signals recorded from the proximal portion of voltage‐clamped presynaptic terminals had a dependence on command potential which was shifted relative to signals recorded from other presynaptic regions. Micro‐electrode measurements of presynaptic membrane potential showed that during voltage‐clamp depolarizations the proximal region was less depolarized than the rest of the presynaptic terminal. This indicates that voltage‐clamped presynaptic terminals may be poorly controlled at their proximal region due to current flow into the adjacent axon. This poor control can cause heterogeneous Ca entry into the presynaptic terminal and thus heterogeneous release of transmitter along the terminal. Application of Ca ions from an extracellular pipette positioned near the distal end of the presynaptic terminal was used to restrict Ca entry to this well‐controlled region. Local Ca application decreased the contribution of release from the poorly controlled proximal region to synaptic transfer curves. Presynaptic Ca currents were derived by correcting membrane currents for leakage and capacitive currents and other currents measured in the absence of Ca application. Ca currents measured in this way activated along a sigmoidal time course and did not inactivate for depolarizations as long as 25 ms. Peak Ca currents occurred at approximately ‐10 mV and inward Ca currents had an apparent 'reversal potential' near +60 mV. Ca channel activation, assessed with tail current measurements, was half‐maximal at ‐13 mV and maximal at +20 mV. Simultaneous measurements of presynaptic Ca currents and Arsenazo III transients revealed a quantitative correspondence between Ca current integrals and Arsenazo III signal amplitude. This suggests that both methods provide reliable measures of Ca ion entry into presynaptic terminals under these conditions.
The effects of pregnancy and parturition on phosphorus metabolites in rat uterus studied by 31P nuclear magnetic resonance.
Authors: Dawson M J , Wray S
Published: December 2014

Concentrations of phosphorus metabolites and intracellular pH have been measured in non‐pregnant, late‐pregnant and post‐partum rat uterus using 31P nuclear magnetic resonance (31P n.m.r.). Intact uterine tissue was superfused with oxygenated de‐Jalon solution at 4, 20 or 37 degrees C while inside the n.m.r. spectrometer. The phosphocreatine concentration [PCr], was higher and the inorganic phosphate concentration [Pi], lower than values determined by chemical analysis of extracts from both pregnant and non‐pregnant rat uterus. [PCr] was 1.4‐fold greater in late‐pregnant than in non‐pregnant rat uterus. Following parturition, large changes were observed in [PCr], [Pi] and in an unidentified metabolite in the phosphomonoester (PME) region of the n.m.r. spectrum. The time course of the recovery of these metabolites to prepregnant values was determined. The [PCr] remained below the non‐pregnant value for at least 1 week post‐partum and the [Pi] was elevated, compared to the non‐pregnant value, during this period. More rapid changes were seen in the [PME], which doubled on day 0 post‐partum but almost returned to its non‐pregnant value on day 1 post‐partum. No significant difference was observed between intracellular pH values in late‐pregnant and non‐pregnant rat uterus; however, there was a large acid shift following parturition. Intracellular pH depended upon the temperature at which the tissue was maintained. The effect of muscular work during parturition was investigated by comparing Caesarian‐sectioned uteri with uteri which had undergone normal parturition. Uteri examined 1 day after Caesarian operation showed no differences in metabolite levels from normal, 1 day post‐partum uteri. We conclude that concentrations of phosphorus metabolites depend upon the physiological state of the uterus. We suggest that the changes following parturition are not a consequence of the mechanical work performed by the uterus, but must be caused by some other event associated with parturition such as hormonal changes.
Discharge patterns of pudendal efferent fibres innervating the external anal sphincter of the cat.
Authors: Krier J
Published: December 2014

Segmental somatic reflexes to pudendal motor axons which innervate the skeletal muscle of the external anal sphincter were studied in cats with an intact spinal cord and in acutely spinalized cats (T13‐L2 spinal cord transection level) during electrical stimulation of afferent fibres in the pudendal nerve, during distension of the anal canal and reproductive organs, and during tactile (light touch and pressure) and nociceptive stimuli (pinch) applied to the mucosa of the anal canal, anal‐perianal skin region, and the skin surrounding reproductive organs. Forty single pudendal motor axons recorded from nerve filaments in the pudendal nerve branch to the external anal sphincter which responded reflexly to electrical stimulation of afferent fibres in the contralateral pudendal nerve were studied. Only one motor axon was spontaneously active. 70% of these motor axons were also activated by distension of the anal canal and reproductive organs and by mechanical stimulation of the skin. 61% of motor axons which were activated by distension of the anal canal were also activated by mechanical stimulation of the mucosa of the anal canal, anal‐perianal skin region. 29% of motor axons were activated by convergent afferent inputs (during distension and mechanical stimulation) from both reproductive organs and from the external anal sphincter region. Motor axons exhibited bursts of action potentials during reflexes initiated during distension of the anal canal and vagina. Motor axons exhibited phasic discharges of action potentials during reflexes initiated by tactile or nociceptive stimuli applied to the mucosa of the anal canal, anal‐perianal skin region and the skin surrounding reproductive organs. The peak firing frequencies of action potentials during mechanical stimulation of the skin ranged from 8 to 35 Hz. The average firing frequencies of action potentials during continuous distension of the anal canal ranged from 4 to 16 Hz.
The role of patterned burst and interburst interval on the excitation‐coupling mechanism in the isolated rat neural lobe.
Authors: Cazalis M , Dayanithi G , Nordmann J J
Published: December 2014

Isolated rat neural lobes were stimulated electrically and the release of vasopressin and oxytocin was measured by radioimmunoassay. The neurohypophyses were stimulated with pulses given at a constant frequency or with a pulse pattern imitating the electrical activity, recorded in vivo, of vasopressin‐ or oxytocin‐containing magnocellular neurones. A single burst recorded from a 'vasopressin' cell with an intraburst mean frequency of 13 Hz evoked more vasopressin release than the same number of stimuli delivered at a constant frequency of 13 Hz. The amount of vasopressin release per pulse was much higher at the beginning than at the end of the burst. Series of bursts given with interburst silent periods released more hormone than bursts delivered without silent periods. The amount of hormone released by four 'vasopressin' bursts was significantly larger with silent periods of 21 s than with shorter intervals. Four pulses were much more effective in promoting hormone release when given with 60 ms interspike intervals at the beginning of each second than when delivered at a constant frequency of 4 Hz. Prolonged stimulation with 'vasopressin' bursts had a greater effect in inducing hormone release than the same number of pulses given in burst delivered at a constant frequency of 13 Hz. After an initial increase the rate of vasopressin release declined rapidly whereas oxytocin release remained elevated for the first 20 min and only then decreased. The release of both vasopressin and oxytocin remained, however, above the release from unstimulated neurohypophyses. 45Ca uptake in the neural lobe was larger when the neurohypophyses were stimulated with vasopressin or oxytocin bursts delivered with silent intervals than when the silent periods were omitted, or when the tissue was stimulated with bursts with the same number of pulses but given at a constant frequency of 13 Hz. In conclusion, it is suggested that the interspike intervals in a burst and the silent intervals between bursts are two important determinants of the effectiveness of the burst pattern in promoting neuropeptide release.
Interaction of the renin‐angiotensin system and the renal nerves in the regulation of rat kidney function.
Authors: Handa R K , Johns E J
Published: December 2014

Stimulation of the renal sympathetic nerves in pentobarbitone anaesthetized rats achieved a 13% reduction in renal blood flow, did not change glomerular filtration rate, but reduced urine flow by 37%, absolute sodium excretion by 37%, and fractional sodium excretion by 34%. Following inhibition of converting enzyme with captopril (0.38 mmol kg‐1 h‐1), similar nerve stimulation reduced both renal blood flow and glomerular filtration rate by 16%, and although urine flow and absolute sodium excretion fell by 32 and 31%, respectively, the 18% fall in fractional sodium excretion was significantly less than that observed in the absence of captopril. Renal nerve stimulation at low levels, which did not change either renal blood flow or glomerular filtration rate, reduced urine flow, and absolute and fractional sodium excretions by 25, 26 and 23%, respectively. In animals receiving captopril at 0.38 mmol kg‐1 h‐1, low‐level nerve stimulation caused small increases in glomerular filtration rate of 7% and urine flow of 12%, but did not change either absolute or fractional sodium excretions. At one‐fifth the dose of captopril (0.076 mmol kg‐1 h‐1), low‐level nerve stimulation did not change renal haemodynamics but decreased urine flow, and absolute and fractional sodium excretions by 10, 10 and 8%, respectively. These results showed that angiotensin II production was necessary for regulation of glomerular filtration rate in the face of modest neurally induced reductions in renal blood flow and was compatible with an intra‐renal site of action of angiotensin II preferentially at the efferent arteriole. They also demonstrated that in the rat the action of the renal nerves to decrease sodium excretion was dependent on angiotensin II.
Ion‐selective micro‐electrode studies of the electrochemical potentials in trout urinary bladder.
Authors: Harvey B J , Lahlou B
Published: December 2014

Intracellular micro‐electrode techniques were used to measure the electrical resistances of the cell membranes and the shunt pathway and intracellular ionic activities in trout urinary bladder when the tissue was incubated in Ringer solution and in the presence of the polyene antibiotic ionophore amphotericin B. In control conditions the transepithelial potential was zero and the intracellular potential was ‐56 mV. The intracellular ionic activities measured with single‐ and double‐barrel ion‐sensitive micro‐electrodes for the first time in a fish bladder (aiNa = 16 mM, aiK = 87 mM, and aiCl = 21 mM) indicate an active accumulation of K and Cl ions and an active extrusion of Na ions by the cell. The maintenance of intracellular Cl activity above its equilibrium value depended on the presence of Na ions in the mucosal medium, but was independent of the presence of K ions. Flat cable analysis yielded values for transepithelial, apical, basolateral and shunt resistances of 197, 2790, 1986 and 205 omega cm‐2 respectively. Equivalent circuit analysis using amphotericin B yielded similar values for shunt resistance. The paracellular pathway accounts for 96% of transepithelial current flow and this epithelium may be classified as 'leaky'. The cells are electrically coupled with a space constant of 354 micron. Amphotericin B when added to the mucosal solution induced an immediate serosa positive transepithelial potential of about 9 mV and a short‐circuit current of 64 microA cm‐2. The Vt was ouabain sensitive and dependent on mucosal Na concentration. The origin of the antibiotic induced transepithelial potential was an increase in the sum of the cell membrane electromotive forces. The apical membrane potential depolarized to ‐7 mV and its resistance fell to 433 omega cm‐2. During the first 10 min of exposure aiNa increased to 80 mM and aiK decreased to 7 mM with only a small change in aiCl. The changes in cellular Na+ and K+ activities were in accordance with their passive redistribution down their electrochemical gradients.
Electrical properties of the light‐sensitive conductance of rods of the salamander Ambystoma tigrinum.
Authors: Baylor D A , Nunn B J
Published: December 2014

The light‐sensitive conductance of isolated rods from the retina of the tiger salamander was studied using a voltage‐clamp method. The membrane current of the outer segment was collected with a suction electrode while the internal voltage was measured and controlled with a pair of intracellular electrodes. Saturating light blocked the outer segment current at all potentials, the residual conductance usually becoming less than 20 pS. This suggests that light‐sensitive channels comprise the main ionic conductance in the surface membrane of the outer segment. Current‐voltage relations determined 10‐40 ms after changing the voltage showed outward‐going rectification, the outward current increasing e‐fold for a depolarization of 11‐14 mV. The reversal potential of the light‐sensitive current was estimated as 5 +/‐ 4 mV. This is consistent with other evidence indicating that the channel is not exclusively permeable to Na. Applying steady light, lowering external Ca, or changing the intracellular voltage to a new steady level scaled the light‐sensitive current without altering the reversal potential or the form of the rectification. This suggests that all three manipulations change the number of channels in the conducting state without changing the ionic concentration gradients or the mechanism of permeation through an 'open' channel. Hyperpolarizing voltage steps slowly increased the light‐sensitive current and depolarizing steps reduced it. A gating variable Y expressing the fractional activation of the light‐sensitive conductance in the steady state was derived from the ratio of the instantaneous and steady‐state currents. Y declined at voltages positive to ‐100 mV and usually reached a minimum near 0 mV, with a secondary rise positive to 0 mV. Around the dark voltage Y changed e‐fold in roughly 25 mV. The voltage‐dependent gating in (6). appeared to involve two delays similar in magnitude to those of the four principal delays in the rod's response to a dim flash. Steady background light shortened the time‐scale of gating and flash responses to a similar degree. Clamping the voltage at the dark level had little effect on the photocurrent evoked by a flash. The small, delayed effect actually observed is explained by the slow voltage‐dependent gating of the light‐sensitive conductance. Hyperpolarization had little effect on the kinetics of the response to a flash, but depolarization slowed the response, causing it to reach a larger, later peak. Depolarization also prolonged the blockage of the light‐sensitive current after a saturating flash.(ABSTRACT TRUNCATED AT 400 WORDS)
Fluid reabsorption by the proximal convoluted tubule of the kidney in lactating rats.
Authors: Arthur S K , Green R
Published: December 2014

Using free‐flow micropuncture techniques, the rate of reabsorption from the proximal convoluted tubules was measured in virgin, 19‐day‐pregnant and 6‐ to 7‐day‐lactating Sprague‐Dawley rats. In separate groups of animals proximal convoluted tubules were filled with silicone rubber, dissected out and their lengths measured. Single nephron glomerular rate was increased in pregnant and lactating animals. The rate of reabsorption per unit length of the proximal convoluted tubule was decreased in pregnant animals but similar in virgins and lactating rats. The proximal convoluted tubule was increased in length in pregnant and lactating animals. As a result the total reabsorption by the proximal convoluted tubule was similar in virgin and pregnant animals but increased in lactating animals. The amount reabsorbed by the loop of Henle and distal parts of the nephron is greater in pregnant and lactating animals than in virgins.
Effect of calcium antagonists on adrenergic mechanisms in canine saphenous veins.
Authors: Jayakody R L , Kappagoda C T , Senaratne M P
Published: December 2014

Experiments were designed to investigate the effect of two calcium antagonists, diltiazem and nicardipine (concentration range: 10(‐7)‐10(‐4) M), on the contractile responses to transmural nerve stimulation, exogenous noradrenaline and tyramine in isolated canine saphenous vein rings. Both diltiazem and nicardipine inhibited the contractile response to transmural nerve stimulation in a non‐competitive, concentration‐dependent manner. At a concentration of 10(‐4) M, diltiazem and nicardipine inhibited the maximum contractile response to transmural nerve stimulation to 0.8 +/‐ 0.8% and 20 +/‐ 10% of control respectively. Effects of diltiazem and nicardipine (up to 10(‐4)M) on the contractile response to exogenous noradrenaline were minimal. The only significant difference observed was a 30% depression of the maximum contractile response with a shift in ED50 at high concentrations of nicardipine. Diltiazem (up to 10(‐4) M) had no significant effect on concentration‐effect curves for tyramine. Nicardipine inhibited the response to tyramine in a non‐competitive manner with the maximum response depressed to 46% of control at 10(‐4) M‐nicardipine. Release of [3H]noradrenaline during transmural nerve stimulation was reduced by both calcium antagonists in a concentration‐dependent manner. However, release of [3H]noradrenaline produced by the indirect sympathomimetic agent tyramine was not significantly inhibited by nicardipine. These experiments suggest that the calcium antagonists diltiazem and nicardipine inhibit the contractile response to transmural nerve stimulation in the canine saphenous vein predominantly by inhibiting the release of endogenous noradrenaline. However, nicardipine appears to have an additional post‐synaptic inhibitory effect on the responses to exogenous as well as endogenous noradrenaline.
Electrophysiological characteristics of neurones in the guinea‐pig deep cerebellar nuclei in vitro.
Authors: Jahnsen H
Published: December 2014

The properties of neurones of the guinea‐pig deep cerebellar nuclei in a slice preparation were investigated by intracellular recording. The recorded population of cells did not differ morphologically from nuclear cells in vivo as judged from neurones stained with Lucifer Yellow. Fifty‐two out of sixty cells were spontaneously active with a regular firing pattern and a mean frequency of 26 +/‐ 14 (mean +/‐ S.D.) impulses/s. The action potentials lasted 0.41 +/‐ 0.07 ms (n = 60) with an amplitude of 58 +/‐ 8 mV. Input resistance was 44 +/‐ 10 M omega and the time constant of the membrane 13 +/‐ 3 ms. When stimulated with intracellularly injected depolarizing current pulses the cells responded with trains of action potentials. Near the threshold for the spike the stimulation produced firing of constant frequency and from more hyperpolarized levels an initial acceleration sometimes followed by a deceleration was seen. At levels less than 15 mV from the spike threshold there was a rebound train of spikes as a response to a hyperpolarizing current injection. At more hyperpolarized levels there was only a small depolarizing potential after the hyperpolarizing stimulation. Three types of subthreshold potentials were recorded. Spikelets rose from base line as 3‐10 mV depolarizing wavelets with a duration between 5 and 10 ms. They served as trigger potentials for the action potential. Plateau potentials were slow depolarizing potentials often reaching the spike threshold and thus generating long trains of action potentials. After‐hyperpolarizations followed each spike with a time course dependent on the previous activity of the cell. Plots of the firing frequency versus injected current were linear at the first and second interspike interval, after 50 ms of activity and at steady state. Plots of the voltage versus injected current were upward concave demonstrating anomalous rectification of the cell membrane. It is concluded that neurones in the deep cerebellar nuclei in vitro are spontaneously active because of the electroresponsive properties of their membranes. The physiological importance may be that the cerebellar output from these cells can be rapidly and efficiently modulated by synaptic potentials generated by Purkinje cells and mossy and climbing fibres.
Projections of oestrogen‐sensitive neurones from the ventromedial hypothalamic nucleus of the female rat.
Authors: Akaishi T , Sakuma Y
Published: December 2014

Stimulation of the mesencephalic central grey matter caused antidromic activation of 199 neurones in the hypothalamic ventromedial nucleus of forty‐six urethane‐anaesthetized female rats, of which twenty‐two (ten ovariectomized and twelve ovariectomized and oestrogen treated) had the lateral projection of the nucleus disrupted by a small parasagittal knife‐cut. The remaining twenty‐four rats (ten ovariectomized and fourteen ovariectomized and oestrogen treated) had a cut in the frontal plane to interrupt caudal projection of the nucleus. In eight animals with the lateral knife‐cut, eighteen cells were antidromically activated from the central grey matter as well as from the dorsal longitudinal fascicle. Collision between the potentials activated from these two sites revealed that seventeen of them descended to the central grey matter by way of the periventricular system, one cell having a bifurcated axon to these sites. Likewise, eleven cells in another group of eight animals with the posterior cut were found to project to the central grey matter via the perifornical region. Pre‐treatment with oestrogen significantly lowered the activation thresholds and absolute refractory periods of neurones antidromically stimulated from the central grey in ovariectomized animals bearing posterior but not lateral knife‐cuts. These results suggest that the ventromedial hypothalamic neurones responsible for oestrogen‐dependent autonomic and behavioural functions project to the central grey via a lateral rather than a posterior pathway.
The effect of a transient outward current (IA) on synaptic potentials in sympathetic ganglion cells of the guinea‐pig.
Authors: Cassell J F , McLachlan E M
Published: December 2014

The responses to stimulation of preganglionic fibres have been studied in sympathetic neurones in ganglia of the caudal lumbar sympathetic chain (l.s.c.) and in the distal lobes of inferior mesenteric ganglia (i.m.g.) isolated from guinea‐pigs. Most l.s.c. neurones were classified as 'phasic' and i.m.g. neurones as 'tonic' (see Cassell, Clark & McLachlan, 1986). The types of preganglionic inputs received by l.s.c. and i.m.g. neurones differed: l.s.c. cells almost invariably received at least one suprathreshold ('strong') input, in addition to several subthreshold ones; i.m.g. neurones more commonly received only subthreshold inputs via the lumbar splanchnic nerves. Prolonged discharges were evoked in some i.m.g. cells by stimulation of lumbar splanchnic nerves at strengths just supramaximal for the conventional fast synaptic responses. These appeared to arise from repetitive discharges evoked in other neurones intrinsic to the i.m.g. The time constants of decay of subthreshold synaptic currents recorded under voltage clamp in l.s.c. neurones (4.9 +/‐ 0.2 ms) were significantly shorter on average than those recorded in tonic i.m.g. cells (7.1 +/‐ 0.3 ms), although the values of time constant for the two populations overlapped. In phasic neurones, excitatory synaptic potentials (e.s.p.s) evoked at resting membrane potential by stimulation of preganglionic axons decayed with the same exponential time course as an electrotonic potential. In tonic neurones, the time course of decay of the e.s.p. was briefer, but always followed an exponential with the same time constant as the cell input time constant over the final part of the response. If tonic neurones were hyperpolarized by the passage of current through the recording micro‐electrode, the time course of decay of the e.s.p. was prolonged and became the same as that of the electrotonic potential. The shape of e.s.p.s in phasic and tonic neurons could be mimicked in a computer model of the neurones incorporating the different activation/inactivation characteristics of the A current (IA) (Cassell et al. 1986) for each neurone type. It is concluded that, in addition to the contribution of IA to the rhythmic firing properties of tonic sympathetic neurones, this current also markedly inhibits the effects of excitatory synaptic conductance changes in this type of ganglion cell.
Estimating the time course of evoked quantal release at the frog neuromuscular junction using end‐plate current latencies.
Authors: Baldo G J , Cohen I S , Van der Kloot W
Published: December 2014

The use of end‐plate current (e.p.c.) latency measurements to estimate the time course of the stochastic probabilistic process governing evoked release was investigated in the sciatic nerve‐sartorius muscle preparation of the frog, Rana pipiens. We also examined the possibility that the release of a quantum depresses or enhances the subsequent release of additional quanta. Muscle end‐plates were voltage clamped at 3‐4 degrees C. Quantal release was restricted to a short, or localized, region of the nerve terminal using Ca2+‐free, EGTA Ringer solution and a Ca2+‐filled micropipette. The number of e.p.c.s containing 0, 1, 2, etc. quanta were totalled and compared to numbers predicted using Poisson's theorem. The differences between the actual and predicted numbers of events were not significant at the nineteen junctions studied (P less than 0.05). The latency of the first quantum observed in several hundred e.p.c.s was measured and used to calculate an estimate, alpha 1(t), of the time‐dependent, probabilistic process, alpha (t), governing all evoked quantal release (Barrett & Stevens, 1972b). In three experiments, all quantal latencies were measured to obtain the actual alpha (t). The alpha 1(t) function gave an excellent approximation of alpha (t) (P greater than 0.2), in real and simulated latency data. The latency of the second quantum in the e.p.c.s was measured and used to provide another estimate, alpha 2(t), of alpha (t). The alpha 2(t) function was lower (depressed) during the first few milliseconds of the evoked release period, relative to alpha 1(t). The difference was significant (P greater than 0.01) in all experiments. Our measurement procedures were tested using computer‐generated 'e.p.c.s' containing randomly occurring 'quanta'. These tests showed that the early depression was due to inadequate detection of the second quantum in the e.p.c.s. The effect of Sr2+ on evoked release was examined using double‐barrelled pipettes containing 1 M‐SrCl2 and CaCl2 solutions. The major result was that the durations of alpha 1(t) and alpha 2(t) were equally lengthened in Sr2+, relative to Ca2+.