bluuebunny/crossref_metadata_2025 huggingface dataset:
A role for an indoleamine other than 5‐hydroxytryptamine in the hypothalamic thermoregulatory pathways of the rat
Authors: Cox B. , Davis A. , Juxon Valerie , Lee T. F. , Martin Deborah
Published: December 2014

1. Intrahypothalamic injection of either 5‐hydroxytryptamine (5‐HT) (20 μg) or tryptamine (1 μg) caused hypothermia and hyperthermia respectively in lightly restrained rats maintained at an ambient temperature of 20 ± 1 °C.

2. Both the 5‐HT‐ and the tryptamine‐sensitive sites were located within the same region of the preoptic area.

3. When rats were tested at different ambient temperatures (4, 20 and 29 °C), intrahypothalamic injection of 5‐HT caused a marked fall in core temperature (‐1·3 °C) in rats maintained at 4 °C, but smaller responses were obtained at 20 and 29 °C (‐0·9 and ‐0·5 °C respectively). Tryptamine caused a significant hyperthermia in rats kept at 20 °C, but had no significant effect in rats maintained at either 4 or 29 °C.

4. The hypothermic effect of 5‐HT was selectively antagonized by systemic pre‐treatment with cyproheptadine (2·5 mg/kg), but not by methergoline (0·625 mg/kg) and methysergide (0·2 mg/kg). In contrast, the hyperthermic effect of tryptamine was blocked by methergoline and methysergide, but not by cyproheptadine.

5. Cyproheptadine (2·5 mg/kg) reduced the ability of rats to cope with a heat load but had no effect on the response to cold. In contrast, methergoline (0·625 mg/kg) and methysergide (0·2 mg/kg) reduced the ability to cope with cold but the rats' ability to cope with a heat load remained intact.

6. These results suggest the existence of two indoleamine pathways within the preoptic anterior hypothalamus involved in the control of body temperature: a serotonergic pathway mediating heat loss and a non‐serotonergic pathway mediating heat gain. The non‐serotonergic system may exert its effects by modulating the activity of a central serotonergic system.
Pharmacological studies of charge movement in frog skeletal muscle.
Authors: Hui C S
Published: December 2014

Charge movements in frog twitch fibres were studied using the three‐microelectrode voltage‐clamp technique. In a solution made moderately hypertonic with 350 mM‐sucrose, fibre contraction was effectively blocked and a secondary hump appeared in the decay phase of the 'on' part of charge movement. At small depolarizations, the hump (Q gamma) is small and slow. As depolarization is increased, Q gamma becomes larger in magnitude and faster in kinetics until it merges with the main part of charge movement (Q beta). As the fibre is perfused extracellularly with a test solution saturated with dantrolene sodium, Q gamma disappears in about 30 min whereas the kinetics of Q beta are slowed down. After equilibration in the dantrolene sodium solution, the total moveable charge is reduced by about 20%, which could very well be the charge carried by Q gamma. Tetracaine also suppresses Q gamma but does not seem to have any effect on the kinetics of Q beta. The suppression of Q gamma appears to be dose‐dependent, with complete abolition occurring at about 4 mM‐tetracaine. Dissection of charge movement with tetracaine indicates that Q gamma might be bell‐shaped and capacitive in nature. Q beta and Q gamma might be two distinct species of charge and Q gamma would probably be more closely associated with calcium release from the sarcoplasmic reticulum.
The calcium dependence of spontaneous and evoked quantal release at the frog neuromuscular junction
Authors: Barton S. B. , Cohen I. S. , van der Kloot W.
Published: December 2014

1. The quantal output from stimulated nerve terminals in the frog sciatic nerve—sartorius muscle preparation in low‐Ca2+ Ringer solution was measured by the coefficient of variation and the failures methods. Adding sucrose to the Ringer to increase the tonicity or adding ethanol increased miniature end‐plate potential (m.e.p.p.) frequency and also the end‐plate potential (e.p.p.) amplitude. Earlier reports suggested that increases in tonicity did not increase evoked quantal release.

2. Concanavalin A has been reported to block the increase in m.e.p.p. frequency caused by increasing the tonicity of the Ringer (Gorio & Mauro, 1979). This effect was confirmed. The lectin‐treated preparations also failed to show an increase in evoked quantal release when the tonicity was increased.

3. A model in which both spontaneous and evoked quantal releases depend on some power of the intracellular [Ca2+] is presented. The model predicts that rises in m.e.p.p. frequency will be accompanied by increased quantal output from stimulated nerve terminals. The maximum slope of the relationship between log (evoked quantal output) and log ([Ca2+]out) will be less than the true power. A theoretical analysis shows that, as the true power approaches infinity, the maximum slope will be slightly above 4. The value for the slope usually found experimentally at the frog neuromuscular junction is also about 4.

4. The model does not fit the experimental data. The observed increases in evoked quantal release are higher than those predicted for the observed increases in spontaneous release. There are several possible explanations for the discrepancy. Treatments that increase m.e.p.p. frequency may also increase Ca2+ influx into the stimulated terminal. However, we prefer the explanation that there is a fraction of spontaneous release that is independent of the [Ca2+] in the terminal; if this is true the model might account for the data.

5. The model can account for a variety of puzzling experimental observations, including: (a) the effect of hypertonic solutions and of diamine in decreasing the slope in the relation between log (evoked quantal output) and log ([Ca2+]out); (b) the slope of near 1 observed at the crustacean neuromuscular junction; (c) the decrease in the slope produced by treatment with botulinum toxin.
Factors determining the level and changes in intra‐articular pressure in the knee joint of the dog.
Authors: Nade S , Newbold P J
Published: December 2014

Intra‐articular pressure levels were determined for joint positions throughout the normal physiological range of movement of dogs' knee joints. Change in joint position resulted in change in intra‐articular pressure. It was demonstrated that intra‐articular pressure is highest with the joint in the fully flexed position. Minimum pressure was recorded at a position between 80 degrees and 120 degrees. Minimum pressures were usually subatmospheric. The rate of change of joint position affected intra‐articular pressure. The relationship of intra‐articular pressure and joint position before and after full flexion demonstrated a hysteresis effect; the pressures were lower than for the same joint position before flexion. Maintenance of the joint in the fully flexed position for increasing periods of time between repeated movement cycles resulted in a similar reduction, of constant magnitude, in pressure between joint positions before and after each period of flexion. However, there was also a progressive decrease in pressure for all joint angles over the total number of movement cycles. There is a contribution to intra‐articular pressure of joint capsular compliance and fluid movement into and out of the joint (both of which are time‐dependent). The recording of intra‐articular pressure in conscious, upright dogs revealed similar pressure levels to those measured in anaesthetized supine dogs. The major determinants of intra‐articular pressure in normal dog knee joints include joint size, synovial fluid volume, position of joint, peri‐articular tissue and joint anatomy, membrane permeability, capsular compliance, and movement of fluid into and out of the joint.
Strength and cross‐sectional area of human skeletal muscle.
Authors: Maughan R J , Watson J S , Weir J
Published: December 2014

The maximum voluntary force (strength) which could be produced by the knee‐extensor muscles, with the knee held at a right angle, was measured in a group of healthy young subjects comprising twenty‐five males and twenty‐five females. Both legs were tested: data from the stronger leg only for each subject were used in the present study. Computed tomography was used to obtain a cross‐sectional image of the subjects' legs at mid‐thigh level, measured as the mid‐point between the greater trochanter and upper border of the patella. The cross‐sectional area of the knee‐extensor muscles was determined from the image obtained by computer‐based planimetry. The subjects' height and weight were measured. An estimate of body fat content was obtained from measurements of skinfold thicknesses and used to calculate lean body mass. Male subjects were taller (P less than 0.001), heavier (P less than 0.001), leaner (P less than 0.001) and stronger (P less than 0.001) than the female subjects. No significant correlation was found to exist between strength of the knee‐extensor muscles and body weight in the male or in the female subjects. In the male subjects, but not in the female group, there was a positive correlation (r = 0.50; P less than 0.01) between strength and lean body mass. Muscle cross‐sectional area of the male subjects was greater than that of the female subjects (P less than 0.001). The ratio of strength to cross‐sectional area for the male was 9.49 +/‐ 1.34 (mean +/‐ S.D.). This is greater but not significantly so, than that for females (8.92 +/‐ 1.11). In both male and female groups, there was a significant (P less than 0.01) positive correlation between muscle strength and cross‐sectional area. A wide variation in the ratio of strength to muscle cross‐sectional area was observed. This variability may be a result of anatomical differences between subjects or may result from differences in the proportions of different fibre types in the muscles. The variation between subjects is such that strength is not a useful predictive index of muscle cross‐sectional area.
The effect of apamin on non‐adrenergic, non‐cholinergic vasodilator mechanisms in the intestines of the cat.
Authors: Jodal M , Lundgren O , Sjöqvist A
Published: December 2014

The effects of apamin, a polypeptide isolated from bee venom, on different vasodilator mechanisms in the small and large intestines were studied in atropinized cats. In the large intestine vasodilatation in response to pelvic nerve stimulation was either abolished or markedly diminished by I.A. apamin. However, neither the contraction of colonic muscle which occurred under these conditions nor sympathetic vasoconstriction was significantly influenced by apamin, suggesting that the effect of the peptide was not a non‐specific effect on nerves or vascular smooth muscle. In the small intestine it was observed that the nervous vasodilatation induced by transmural electrical field stimulation or mechanical mucosal stimulation was either diminished or abolished by apamin. Intestinal vasodilatation, caused by close I.A. infusions of 5‐hydroxytryptamine (5‐HT), was abolished by apamin. After giving apamin 5‐HT infusions induced a vasoconstriction in five out of six experiments. Vasodilatation induced by vasoactive intestinal polypeptide (VIP) was not significantly affected by apamin. In a series of in vitro experiments on rat portal vein, dose‐response curves of several putative intestinal neurotransmitters were determined in the presence and absence of apamin. The following substances were tested: VIP, substance P, bradykinin, 5‐HT, ATP and adenosine. Apamin had no effect on the dose‐response curves of any of these compounds. The results are discussed in relation to the possibility that apamin may act by blocking the release of a putative peptidergic transmitter from nerve terminals.
Plasma vasopressin concentration in the anaesthetized dog before, during and after atrial distension.
Authors: Ledsome J R , Ngsee J , Wilson N
Published: December 2014

Plasma vasopressin (AVP) concentration in dogs anaesthetized with chloralose was measured by radioimmunoassay and was within the range of 2‐5 pg/ml. during control periods. Distension of the left atrium led within 2 min to a fall in plasma AVP concentration which reached a steady lower value within 4 min. After cessation of atrial distension the AVP concentration returned to pre‐distention values within 4 min. Cooling the cervical vagosympathetic nerves to 8‐10 degrees C led to a rise in plasma AVP concentration. Atrial distension during cooling of the vagi resulted in a further increase of plasma AVP concentration.
Measurement of intracellular calcium ions and oxygen radicals in polymorphonuclear leucocyte‐erythrocyte ‘ghost’ hybrids.
Authors: Campbell A K , Hallett M B
Published: December 2014

Sendai virus induced fusion between rat polymorphonuclear leucocytes and human erythrocyte ‘ghosts’ containing the Ca‐activated photoprotein obelin. This resulted in the production of more than 90% of the cell population as viable hybrid cells, containing active photoprotein. Substances entrapped originally within the ‘ghosts’ could be transferred to the hybrids as shown morphologically by fluorescence microscopy, and immunologically by the use of antibodies specific for each of the cell types. Resting free Ca2+ in the hybrids was estimated to be 0.1‐0.3 microM. The relationship between intracellular Ca2+ within the hybrids and the production by the hybrids of oxygen radicals, as measured by luminol chemiluminescence, was investigated. The Ca ionophore A23187 stimulated both a rise in intracellular Ca2+ and oxygen radical production, the maximum rate of oxygen radical production being dependent upon the intracellular Ca2+ concentration. Complement activation at the cell surface, chemotactic peptide, and concanavilin A stimulated a rise in intracellular Ca2+, each with different characteristics: complement activation increased intracellular Ca2+ to 8 microM for at least 60 sec; chemotactic peptide raised it to approximately 0.6 microM for a prolonged period (at least 10 min) and concanavilin A stimulated a transient (t1/2 = approximately 80 sec) rise to approximately 0.6 microM. Un‐opsinized particles, latex beads (diam. approximately equal to 1 micron), which stimulate oxygen radical production, did not produce a detectable rise in intracellular Ca2+. Intracellular EGTA (approximately, 2.5 mM) inhibited both the oxygen radical production and the rises in intracellular Ca2+ induced by chemotactic peptide and concanavilin A, and delayed both the rise in intracellular Ca2+ and the onset of oxygen radical production induced by complement. Intracellular EGTA had no effect on oxygen radical production stimulated by latex particles. An increase in intracellular Ca2+ triggered oxygen radical production by the hybrids in response to the following stimuli: concanavilin A, chemotactic peptide, complement and the Ca ionophore A23187. However, the extent and duration of the increase in cytoplasmic Ca2+ was different for each stimulus, and the apparent relationship between cytoplasmic Ca2+ and oxygen radical production was different for each stimulus. Un‐opsinized particles stimulated oxygen radical production without requiring a rise in intracellular Ca2+ concentration.
Kinetics of glucose transport in human erythrocytes.
Authors: Brahm J
Published: December 2014

The rate of unidirectional D‐[14C]glucose efflux from human red blood cells was determined at self‐exchange and net‐efflux conditions by means of the Millipore‐Swinnex filtering technique and the rapid continuous flow tube technique with which initial rates can be measured within fractions of a second. Determinations at 38, 25 and 10 degrees C of the concentration dependence of glucose self‐exchange flux and net efflux showed that both self exchange and net efflux followed simple Michaelis‐Menten kinetics at all temperatures. At 38 degrees C the maximal self‐exchange flux and the maximal net efflux were identical (6 X 10(‐10) mol/cm2.sec). The cellular glucose concentration for half‐maximal flux (K1/2) was 6.7 mM for self exchange and 8.2 mM for net efflux. By lowering temperature the maximal glucose self‐exchange flux progressively exceeded the maximal net efflux, and was about three times larger at 10 degrees C. K1/2 for self exchange increased to 12.6 mM at 10 degrees C, while K1/2 for net efflux decreased to 4.4 mM. At 38 degrees C the glucose permeability at self exchange at a constant extracellular glucose concentration of 40 mM showed a bell‐shaped pH dependence between pH 6 and pH 9. A maximum was found at pH 7.2, whereas the apparent permeability coefficient was halved both at pH 6 and pH 9. The temperature dependence of glucose transport was determined between 47 and 0 degrees C at a cellular glucose concentration of 100 mM which ensured greater than 85% saturation of the glucose transport system within the temperature range. The Arrhenius activation energy of glucose transport was not constant. By lowering the temperature, the activation energy increased gradually for net efflux from 55 kJ/mole between 38 and 47 degrees C to 151 kJ/mole between 0 and 10 degrees C. The temperature dependence of self‐exchange flux showed a more pronounced change around 10 degrees C. The Arrhenius activation energy was found to be 61 kJ/mole above and 120 kJ/mole below 10 degrees C.
Blockade of cholinergic channels by chlorisondamine on a crustacean muscle.
Authors: Lingle C
Published: December 2014

Details of the blocking action of chlorisondamine, a ganglionic nicotinic blocker, on the excitatory cholinergic currents of the spiny lobster gastric mill 1 (g.m.1) muscle are described. The steady‐state block of cholinergic ionophoretic currents produced by chlorisondamine is strongly voltage‐dependent. During a hyperpolarizing voltage step, a sequence of ionophoretic agonist pulses in the presence of chlorisondamine shows a large interpulse interaction manifested as a gradual diminution in response amplitude. The extent of diminution is dependent on the number of the pulse in a series and not on the duration of the interval between pulses. The slowly developing blockade is entirely dependent on agonist application. If agonist application is suspended for various time intervals following the development of a given blocked level in chlorisondamine, no recovery from the block is observed whether the rest interval is at the step potential or at more depolarized potentials. Recovery from a given blocked level can be observed if, during a depolarizing voltage step (to ‐60 mV) away from the potential at which the block was established (‐140 mV), agonist is applied before return to the initial potential (‐140 mV). Chlorisondamine produces a dose‐dependent reduction in excitatory junctional current (e.j.c.) decay rate that is linear with chlorisondamine concentration and markedly dependent on voltage (approximately equal to 35 mV/e‐fold change). Reduction in the amplitude of e.j.c.s occurred at concentrations of chlorisondamine that produced no detectable effect on e.j.c. decay. Alterations in e.j.c. amplitude showed time‐ and use‐dependent aspects similar to those observed for ionophoretic currents. These results are discussed primarily in terms of a sequential model in which, following the binding of chlorisondamine to the opened ion channel, the channel can undergo a transition to a stable‐blocked state that requires reactivation by agonist to become unblocked. This stable‐blocked state is considered a closed‐blocked channel.
The charge carried by single‐channel currents of rat cultured muscle cells in the presence of local anaesthetics.
Authors: Neher E
Published: December 2014

Acetylcholine‐induced single‐channel currents were measured in the presence of the lignocaine derivative QX222. Unit responses appeared as bursts of short current pulses as a result of the fast blocking action of the drug (QX222). The amplitude of the individual current pulses was not changed by the presence of the drug up to a concentration of 250 microM. The time integral of current during a burst, which for a sequential blocking model should be independent of drug concentration, decreased at concentrations of QX222 higher than 40 microM. The distribution of gap times within a burst could not be fitted by a single exponential for high concentrations of QX222. It is concluded that the simple sequential model of channel blockade does not apply for concentrations of QX222 higher than 40 microM.
Inferior olive inactivation decreases the excitability of the intracerebellar and lateral vestibular nuclei in the rat.
Authors: Benedetti F , Montarolo P G , Strata P , Tempia F
Published: December 2014

In rats under sodium pentobarbitone anaesthesia the inferior olive region has been reversibly inactivated by applying a cooling probe to the ventral surface of the medulla. Unitary activity has been recorded from the fastigial, interpositus and Deiters nuclei. Identification of units was based on the presence of a dye spot, left by the recording micropipette. In the Deiters nucleus, an additional criterion of identification was the antidromic activation from spinal cord stimulation. Following cooling of the inferior olive of one side, we have observed suppression of the activity of all the fourteen Deiters neurones and of seventeen out of twenty neurones recorded from the intracerebellar nuclei. In two out of seven Deiters neurones tested the antidromic invasion elicited by spinal cord stimulation was suppressed. In rats, whose inferior olive was previously destroyed, cooling of the inferior olive region was not followed by the powerful depression of spike activity seen in the vestibular and cerebellar nuclei cells in the intact rats. These results indicate that the olivocerebellar system is very important in regulating the level of excitability of the subcerebellar structures and therefore in controlling both postural mechanisms and the processing of information relating to sensorimotor integration.
Reserpine has a direct action as a calcium antagonist on mammalian smooth muscle cells.
Authors: Casteels R , Login I S
Published: December 2014

The effects of reserpine on excitation‐contraction coupling and 45Ca exchange of smooth muscle cells of the rabbit ear artery and the guinea‐pig taenia coli have been studied. Reserpine inhibited the spontaneous mechanical activity of the taenia coli and the force development induced by 59 mM‐external K or 10(‐5) M‐carbachol. In the ear artery reserpine blocked the K‐induced contraction but its effect on the contraction elicited by noradrenaline was smaller. At 0.2 mM‐Ca, the inhibition of the tonic component of the noradrenaline‐induced contraction was more pronounced than that of the phasic component. This reserpine action was fully reversible for the noradrenaline stimulus in the ear artery but less so for K‐induced contractions. The inhibitory action on contractions induced in taenia coli by K‐rich solution and by carbachol was even less reversible. The analysis of the effect of reserpine on the 45Ca exchange in the ear artery has revealed that it inhibits the increase of the fractional loss induced by K depolarization, but that it does not exert a significant effect on the increased fractional loss induced by 10(‐5) M‐noradrenaline. Reserpine slows down the filling with 45Ca of the agonist‐sensitive store without affecting the steady‐state amount of Ca taken up by the store. A study of the degree of filling of the store by measuring the force development and the 45Ca release elicited by noradrenaline in Ca‐free medium, reveals that the force development after loading in a reserpine‐containing medium remains less than the control, although the same amount of Ca is released from the store. It was shown by using tetrabenazine that the inhibitory action of reserpine on the Ca exchange and the force development is not due to an interaction of reserpine with the receptor molecules that are responsible for its depleting action on aminergic granules. These results strongly suggest that reserpine exerts a Ca antagonistic action on smooth muscle whereby it blocks the potential‐dependent channels. However, reserpine also affects the receptor‐operated channels to some extent and in addition at a high concentration it seems to exert an unspecific inhibitory action on the contractile system.
Evidence for a cholinergic inhibitory feed‐back mechanism in the rabbit retina.
Authors: Cunningham J R , Dawson C , Neal M J
Published: December 2014

The effects of muscarine, atropine and nicotinic antagonists on the light‐evoked release of radioactivity from rabbit retinas previously exposed to [3H]choline (Ch) was studied. On the basis of previous experiments, this light‐evoked release of total radioactivity was taken as a measure of the light‐evoked release of [3H]acetylcholine (ACh) from the cholinergic amacrine cells. Atropine (1 microM) in the presence, but not the absence, of eserine more than doubled the light‐evoked release of [3H]ACh. Eserine (30 microM) itself had no significant effect on either the spontaneous resting release or the light‐evoked release of [3H]ACh. Muscarine (10 microM) in the presence or absence of eserine reduced the light‐evoked release of [3H]ACh from the retina by 50%. This effect of muscarine was blocked by atropine used in the absence of eserine. The nicotinic antagonists pempidine, hexamethonium and gallamine had no significant effect on retinal [3H]ACh release. Strychnine (20 microM), which alone had no effect on retinal [3H]ACh release, abolished the effects of both muscarine and atropine on the light‐evoked release of [3H]ACh. Bicuculline (5 microM) did not affect the actions of muscarine or atropine on the light‐evoked release of [3H]ACh. Previous experiments had shown that glycine and gamma‐aminobutyric acid (GABA) reduce the light‐evoked release of [3H]ACh from the retina and that these inhibitory effects are selectively blocked by strychnine (20 microM) and bicuculline (5 microM) respectively. These results suggest the presence in the retina of a cholinergic inhibitory feed‐back mechanism which involves a neuronal loop, rather than presynaptic or post‐synaptic inhibitory muscarinic receptors on the cholinergic amacrine cells themselves. Our experiments do not provide evidence on the nature of the proposed inhibitory loop, except that it apparently includes a glycinergic or taurinergic (amacrine) cell.
Aldosterone on sodium transport of rat distal colon in long‐term adrenalectomy during acute and chronic substitution
Authors: Horster Michael , Lückhoff Andreas
Published: December 2014

1. The influence of aldosterone upon water and sodium transport properties of the distal colon was studied in long‐term adrenalectomy (11‐29 days).

2. Six groups of rats were used: I, normal (control); II, adrenalectomized; III, adrenalectomized, acutely substituted with aldosterone (200 μg/kg 4 h); IV, adrenalectomized rats receiving aldosterone simultaneously with the specific inhibitor spironolactone (40 mg/kg within 4 h); V, adrenalectomized, substituted chronically with aldosterone (2 × 75 μg/kg day); VI, adrenalectomized, substituted chronically with dexamethasone (120 μg/kg day).

3. Distal colon segments were perfused in vivo with isotonic Ringer solution. In addition, a hypotonic electrolyte solution (Na+ 111 mM) was used in groups I and II.

4. In adrenalectomy (group II), net water absorption (Jv) was significantly decreased from (normal) 54·4 μl/h cm2±10·5 (n = 9) to 41·2 μl/h cm2±7·3 (n = 4), and net Na+ absorption (JNa) was decreased from 13·6 μmol/h cm2+3·5 to 8·5 μmol/h cm2±0·9 (isotonic perfusate). Similarly, Jv was decreased from 54·0 μl/h cm2±8·3 (n = 4) to 37·3 μl/h cm2±4·2 (n = 7), and JNa from 8·6 μmol/h cm2±2·1 to 4·2 μmol/h cm2±2·1 (hypotonic perfusate).

5. Acute aldosterone substitution in adrenalectomy (III) had no effect upon Jv (37·1 μl/h cm2±10·3; n = 5) but increased JNa to 10·3 μmol/h cm2±0·3.

6. The luminal Na+ steady‐state concentration was higher in group II (11·2 mmol l−1±3·6; n = 6) than in group I (3·3 mmol l−1±1·4; n = 29). Acute aldosterone substitution restored this value to normal (3·0 mmol l−1±1·2; n = 4). The aldosterone effect was partly blocked by spironolactone: the Na+ steady‐state concentration was 6·4 mmol/l±0·6 (n = 3) in group IV.

7. At the steady‐state luminal Na+ concentration, the osmotically driven net water fluxes were not different in groups I and II, indicating that the hydraulic permeability coefficient is not altered in adrenalectomy.

8. In group V, Jv (54·9 μl/h cm2±10·9; n = 7) and JNa (11·9 μmol/h cm2±1·7; n = 6) were not significantly different from normal.

9. In group VI, Jv (37·3 μl/h cm2±6·0; n = 5) and JNa (8·0 μmol/h cm2±1·4) were not significantly different from group II.

10. The mineralocorticoid effects of aldosterone in long‐term adrenalectomy appear to represent the principal determining factors of colonic Jv and JNa.
The effect of pregnancy and lactation on the mesometrium of the rat.
Authors: Wray S
Published: December 2014

Weight and collagen content of the mesometrium, that part of the reproductive tract which lies between the uterus and the body wall, were measured in the rat, throughout pregnancy and post‐partum. Both the weight and the collagen content increased significantly during pregnancy and decreased rapidly after parturition, the collagen content halving in around four days. The changes were almost entirely in the part of the mesometrium between the main longitudinal blood vessels and the uterus. At any given stage of pregnancy, the larger the uterus, the larger were both the weight and collagen content of the mesometrium. In rats pregnant in only one uterine horn the mesometrium associated with the barren horn showed no changes in weight or collagen content during pregnancy. Removal of fetuses from one uterine horn reversed the growth of the mesometrium associated with that horn, but not the growth of the mesometrium associated with the other (pregnant) horn. Cutting the attachment to the body wall prevented mesometrial growth during pregnancy although the tissue remained attached to the uterus, with its blood supply and the metrial gland intact. These data suggest that mesometrial growth in pregnancy is stimulated by stretch associated with the pregnant uterine horn.
Uptake, storage and secretion of 5‐hydroxytryptamine and its amino acid precursor by dispersed rat pancreas acinar cells.
Authors: Stern L , Tenenhouse A , Yu E W
Published: December 2014

Rat pancreas acinar cells contain 5‐hydroxytryptamine (5‐HT; 10.86 +/‐ 2.52 ng/i.u. amylase), all of which can be accounted for by the 5‐HT recovered from the zymogen granule fraction of these cells (10.70 +/‐ 3.06 ng/i.u. amylase). When incubated with [14C]5‐HT dispersed acinar cells take up the amine and concentrate it in zymogen granules. These cells will also take up [14C]5‐HTP (5‐hydroxytryptophan), decarboxylate it and store the [14C]5‐HT so produced in zymogen granules. 5‐HTP itself is not taken up by the granules. 5‐HT is incorporated into zymogen granules early in their formation; no amine is accumulated by mature zymogen granules and the amine within the mature granule is not exchangeable with extragranular amine. When dispersed acinar cells pre‐labelled with [14C]5‐HT and [3H]leucine are stimulated with caerulein, there is a synchronous increase in amylase activity and secretion of [14C]5‐HT and [3H]protein; the ratios of [3H]protein/[14C]5‐HT in zymogen granules and in the secretory products are identical. Pancreas acinar cells take up L‐DOPA, decarboxylate it and store the dopamine produced in zymogen granules but the dopamine is not retained by the granules (t1/2 approximately equal to 90 min) and dopamine secretion from cells exposed to caerulein could not be demonstrated. It is concluded that 5‐HT is a normal component of rat pancreas acinar cell zymogen granule. The granular amine has a turnover rate similar to that of granular protein and is released when the cells are stimulated to secrete protein. All the 5‐HT released from the cell originates in zymogen granules.
The spatial distribution of excitability and membrane current in normal and demyelinated mammalian nerve fibres.
Authors: Bostock H , Sears T A , Sherratt R M
Published: December 2014

Thresholds to electrical stimulation have been recorded, concurrently with the membrane currents of conducted impulses, at many positions along undissected single fibres in rat spinal roots. In normal myelinated fibres, distinct threshold minima invariably coincided with sites of inward current generation, and were therefore identified as nodes of Ranvier. Between nodes, the thresholds rose by an order of magnitude. At normal nodes, the charge thresholds were linearly related to stimulus duration, as predicted by computer simulations of a model myelinated fibre (Bostock, 1983). The strength‐duration time constants averaged 64.9 +/‐ 8.3 microseconds (mean +/‐ S.D.) at 37 degrees C, and had a Q10 of 1/1.39. They were relatively insensitive to changes in inter‐electrode distance, or to partial anaesthetization with tetrodotoxin. In fibres treated with diphtheria toxin 6‐8 days previously, to induce paranodal or segmental demyelination, threshold minima were found both at nodes and in internodal regions generating inward membrane current. In these fibres strength‐duration curves were of the same general form as at normal nodes, but with strength‐duration time constants increased at widened nodes (up to 350 microseconds) and at excitable internodes (600‐725 microseconds). Comparison with the computer model indicated that these changes were most likely due to exposure of axon membrane with a time constant much longer than that of the normal nodal membrane. In none of the demyelinated fibres examined have we found any evidence of hyperexcitability.
Effects of chronic hyperprolactinaemia on experimentally induced thirsts in male rats.
Authors: Katovich M J , Simpkins J W
Published: December 2014

Chronic hyperprolactinaemia was induced in ten male Wistar rats by subcutaneous injection of tissue fragments of the MtTW 15 prolactin‐secreting adenoma. Serum prolactin was elevated significantly by 3 weeks after adenoma inoculation and increased progressively thereafter. An additional ten Wister‐Furth rats were inoculated with the MtTW 15 adenoma and an equal number of age‐matched controls were used to evaluate the drinking response to several dipsogenic agents. The hyperprolactinaemic rats consumed twice as much water as did control rats over a 24 hr period. Administration of the beta‐adrenergic agonist, isoprenaline (25 micrograms/kg, s.c.), resulted in a similar increase in water intake in both groups prior to an elevation in serum prolactin. However, as serum prolactin increased there was a corresponding significantly attenuated dipsogenic response to isoprenaline. Chronic hyperprolactinaemia did not alter the drinking response to angiotensin II (200 micrograms/kg, s.c.), to 24 hr of dehydration or to administration of hypertonic (1 M) saline. These results indicate that chronic hyperprolactinaemia selectively attenuates the dipsogenic response to beta‐adrenergic stimulation and support an involvement of prolactin in modifying the responsiveness of the beta‐adrenergic system.
Apical membrane permeability and kinetic properties of the sodium pump in rabbit urinary bladder.
Authors: Lewis S A , Wills N K
Published: December 2014

Previous studies have shown that aldosterone stimulates the rate of Na+ transport across the rabbit urinary bladder epithelium by increasing the apical membrane permeability to Na+. Paradoxically, ion‐sensitive and conventional micro‐electrode measurements demonstrated that intracellular Na+ activity aiNa+ was essentially unchanged by aldosterone, i.e. aiNa+ was constant regardless of the rate of Na+ transport. The present study was designed to resolve this apparent contradiction. The effects of elevated, endogenous aldosterone levels produced by low‐Na+ diet (Lewis & Diamond, 1976) on urinary bladder Na+ transport were investigated in vitro using Ussing‐type chambers and intracellular conventional and ion‐sensitive microelectrodes. Apical membrane selectivity and kinetics of the Na+ pump were assessed as a function of hormone stimulation. The aldosterone‐stimulated increase in Na+ transport was accounted for by increases in both the relative selective permeability of the apical membrane to Na+ and an increase in its absolute Na+ permeability. The kinetics of the Na+ pump were evaluated electrically by loading the cells with Na+ (monitored with Na+‐sensitive micro‐electrodes) or alternatively by manipulating serosal solution K+ concentration and measuring changes in the basolateral membrane electromotive forces and resistance. From these measurements the current generated by the pump was calculated as a function of intracellular Na+ or extracellular K+. The kinetics of the pump were not altered by aldosterone. A model of highly co‐operative binding estimated Km for Na+ as 14.2 mM and 2.3 mM for K+. Hill coefficients for these ions were 2.8 and 1.8, respectively, consistent with a pump stoichiometry of 3 Na+ to 2 K+. The kinetic properties of the Na‐K pump indicate that physiological levels of aiNa+ are poised at the foot of a step kinetic curve which energetically favours Na+ extrusion.
Asymmetrical charge movement in slow‐ and fast‐twitch mammalian muscle fibres in normal and paraplegic rats.
Authors: Dulhunty A F , Gage P W
Published: December 2014

Asymmetrical charge movements (Q) were recorded from the voltage‐clamped ends of muscle fibres in extensor digitorum longus (e.d.l.) and soleus muscles from rats. Tetracaine (2 mM) was added to solutions to prevent contraction. In both muscles the relationship between Q and membrane potential (V) was S‐shaped and could be described by the Boltzmann‐type equation Q = Qm/(1 + exp[‐(v ‐ V)/k]) where Qm was the maximum charge, V the membrane potential at which Q = Qm/2, and k a ‘slope factor'. On average, Qm was 5‐6 times greater in e.d..l. than in soleus fibres and charge movement occurred at more negative potentials in soleus than in e.d.l. fibres, V being ‐36.7 mV in the former and ‐19.0 mV in the latter, a difference of about 18 mV. The threshold for contraction, determined using a two‐electrode voltage clamp, was more negative in soleus than in e.d.l. fibres. For 500 ms depolarizations, the difference was 12 mV. The relationship between tension and membrane potential during potassium contractures was S‐shaped and, when fitted by the Boltzmann‐type equation, gave V values of ‐25 mV for soleus and ‐14 mV for e.d.l. fibres. In paraplegic rats, the threshold for contraction in soleus fibres shifted about 12 mV to more positive potentials, but there was no change in e.d.l. fibres so that there was no significant difference between the two muscles. In paraplegic rats the relationship between tension and membrane potential during potassium contractures also shifted to more positive potentials in soleus fibres, whereas there was no change in e.d.l. fibres. These changes in the voltage sensitivity of contractile activation in soleus fibres from paraplegic rats were associated with a parallel shift in the voltage sensitivity of charge movement so that the average V shifted from ‐36.7 mV in normal rats to a value of ‐14.2 mV in paraplegic rats. There was also a four‐fold increase in Qm in soleus fibres from paraplegic rats. The difference between the voltage sensitivity of contractile activation and charge movement in e.d.l. and soleus fibres in normal rats supports the hypothesis that the two are closely related: even stronger support comes from the observation of the parallel shift in the voltage sensitivity of contractile activation and charge movement in soleus fibres in paraplegic rats.
Spatio‐temporal interactions in cat retinal ganglion cells showing linear spatial summation.
Authors: Enroth‐Cugell C , Robson J G , Schweitzer‐Tong D E , Watson A B
Published: December 2014

The spatio‐temporal characteristics of cat retinal ganglion cells showing linear summation have been studied by measuring both magnitude and phase of the responses of these cells to drifting or sinusoidally contrast‐modulated sinusoidal grating patterns. It has been demonstrated not only that X cells behave approximately linearly when responding with amplitudes of less than about 10 impulses/sec to stimuli of low contrast but also that cells of another type with larger receptive field centres (Q cells) behave approximately linearly under the same conditions. These Q cells appear to form a homogeneous group which is probably a subset of the tonic W cells (Stone & Fukuda, 1974) or sluggish centre‐surround cells (Cleland & Levick, 1974). The over‐all spatio‐temporal frequency characteristics of cells showing linear spatial summation are not separable in space and time. The form of the spatial frequency responsivity function of these cells depends upon the temporal frequency at which it is measured while the temporal phase of their resonse measured at any constant temporal frequency depends upon the spatial frequency of the stimulus. The behaviour of X and Q cells is quite well explained by an extension of the model in which signals from centre and surround mechanisms with radially Gaussian weighting functions are summed to provide the drive to the retinal ganglion cell. While the general form of the temporal frequency response characteristics of these ganglion cells are probably provided by the characteristics of elements common to the centre and surround pathways, the spatio‐temporal interactions can be explained by assuming that the surround signal is delayed relative to the centre signal by a few milliseconds.
Comparison of birefringence signals and calcium transients in voltage‐clamped cut skeletal muscle fibres of the frog.
Authors: Kovács L , Schümperli R A , Szücs G
Published: December 2014

The characteristic features of birefringence and calcium transients were compared in voltage‐clamped cut skeletal muscle fibres: Birefringence signals were measured by introducing crossed polarizers above and below the fibres (+/‐ 45 degrees to the fibre axis) and using light of 790 nm. Calcium transients were monitored by the metallochromic indicator dye, Antipyrylazo III recording the changes in fibre absorbance at 720 nm. The dye entered the myoplasmic space by diffusion through the cut end. The early large birefringence signals, related to excitation‐contraction coupling had a time course similar to that of calcium transients. The two signals had superimposable onset but the change in optical retardation peaked later and declined more slowly than the calcium signal. Using depolarizing pulses with increasing amplitudes both transients showed the same voltage dependence in the rate of rise, the time‐to‐peak and the peak amplitude. Birefringence signals recorded at different voltages along the strength‐duration curve for contraction threshold had the same amplitudes and similar time constants for the falling phase comparable to the properties of the calcium transients. After applying dantrolene sodium both signals were reduced to the same extent. A shift in the contraction threshold was found towards more positive membrane potential values. The birefringence and calcium transients recorded at the new contraction threshold during the dantrolene treatment showed nearly the same size and time course as threshold transients obtained before the treatment. A subthreshold concentration of caffeine increased the peak amplitude of birefringence signals at a given voltage and decreased the latency of the signals. Birefringence transients at the new contraction threshold under caffeine were smaller than controls. Both effects are very similar to the changes in calcium transients due to caffeine treatment as previously reported. Consequently the voltage‐dependent properties of birefringence and calcium transients and their responses to caffeine and dantrolene treatment are nearly the same. These results support the view that the changes in optical retardation of the fibres reflect calcium bound to some sarcoplasmic binding site rather than a potential change of the sarcoplasmic reticulum.
Long‐term potentiation in commissural and Schaffer projections to hippocampal CA1 cells: an in vivo study in the rat.
Authors: Bliss T V , Lancaster B , Wheal H V
Published: December 2014

Rats were given unilateral injections of kainic acid into the lateral ventricle to produce a unilateral lesion of CA3 pyramidal cells in the hippocampus. This procedure allowed the commissural and associational Schaffer projections of the surviving contralateral CA3 field to be studied separately for their ability to sustain long‐term potentiation (l.t.p.) of synaptic efficacy. Both Schaffer and commissural projections showed l.t.p. of the population excitatory post‐synaptic potential (e.p.s.p.) and the population spike. No significant difference was seen in the degree or duration of l.t.p. sustained by the two projections.
Autogenetic inhibition of extensor gamma‐motoneurones revealed by electrical stimulation of group I fibres in the cat.
Authors: Noth J
Published: December 2014

Forty functionally single gamma‐efferents (20‐42 m/s) to the triceps surae were isolated in ventral root filaments of the decerebrated and paralysed cat in order to study the effects of group I muscle afferents on their own fusimotor neurones. All the efferents studied were spontaneously active. During splitting the continuity of the efferent fibre was preserved so that the destination of the target muscle of the efferent could be determined by antidromic stimulation of the muscle nerve using the collision block technique. Thereafter the filament was cut so that the reflex response, uncontaminated by antidromic impulse invasion, could be recorded from the central end. Sixteen of forty gamma‐efferents to the triceps were inhibited by repetitive stimulation (range ‐3 to ‐40 impulses/s) of the homonymous nerve within the group I range. Raising the stimulus strength above the group II threshold produced no further increase in inhibition. Twelve of these sixteen cells were also tested by stretching the triceps; ten showed marked inhibition, and two were not influenced. In ten of the sixteen inhibited cells, the autogenetic inhibition at maximum group I stimulus strength was larger than the maximum antidromic inhibition elicited by stimulation of the remainder of the cut ventral roots L7 and S1. Since both effects were additive, it is concluded that Renshaw inhibition is at least not solely responsible for the autogenetic inhibition. Consistent with this assumption is the observation that some cells receiving electrically evoked autogenetic inhibition were not susceptible to inhibition induced by small‐amplitude vibration of the triceps. Since small‐amplitude vibration is known to excite most of the Ia afferents of the vibrated triceps, Ib afferents must be involved in the autogenetic fusimotor inhibition. A contribution of Ia afferents to the autogenetic inhibition (via alpha‐motoneurones and Renshaw cells or via Ib inhibitory interneurones) seems likely since inhibition, induced by small‐amplitude vibration, was detectable in many of the cells receiving autogenetic group I inhibition. All of these cells were susceptible to antidromic inhibition. Ten of the forty cells tested responded with tonic facilitation to the homonymous nerve stimulation. Some arguments favour the view that static gamma‐motoneurones are involved in the low‐threshold autogenetic inhibition. The results strongly support earlier work suggest a regulatory function of low‐threshold muscle receptors on their own gamma‐motoneurones.