bluuebunny/crossref_metadata_2025 huggingface dataset:
Synaptic transfer of rod signals to horizontal and bipolar cells in the retina of the toad (Bufo marinus).
Authors: Belgum J H , Copenhagen D R
Published: December 2014

1. Simultaneous intracellular recordings of responses to light flashes were obtained from rod‐horizontal cell and rod‐hyperpolarizing bipolar cell pairs in isolated retinae of the toad. The gain and temporal filtering of synaptic transfer were characterized throughout the rods' range of light responses. 2. Paired rod‐horizontal cell and rod‐bipolar cell responses to dim flashes (less than 0.4 Rh*, where Rh* denotes effective photoisomerizations per rod per flash) exhibited nearly the same time course. Analysis of the onset of the horizontal cell responses revealed a temporal lag equivalent to a single stage of low‐pass filtering (tau f = 75‐200 ms). No filtering was discerned in the transfer of dim‐flash responses from rods to bipolars. On average, horizontal cells were five times as sensitive (mV/Rh*) and hyperpolarizing bipolar cells 10.7 times as sensitive as their paired rods. 3. For brighter flashes, up to 1600 Rh*, the rising and return phases of bipolar responses appeared to be simple scaled versions of the rod responses. The scaling factor was equal to the ratio of flash sensitivities for dim flashes. Rod responses greater than about 2 mV produced a saturation of the bipolar cell response. 4. The return phases of the horizontal cell responses were kinetically similar, scaled versions of the rod responses for rod potentials less than about 5 mV. However, the rising phases lagged significantly behind those of the rod. The effective time constant of the lag increased proportionally with flash intensity. For the brighter flashes, the horizontal cell response peaked as much as a second after the rod response. 5. The linear scaling, minimal temporal filtering and saturation of the bipolar cell responses were satisfactorily reproduced by a model of synaptic transfer that assumed that the rate of transmitter release followed the rod voltage exponentially and that the postsynaptic conductance followed Michaelis‐Menten saturation (Falk & Fatt, 1972). 6. The progressively longer lag in the horizontal cell responses to brighter flashes was satisfactorily simulated by a kinetically limited Falk and Fatt model which postulated that the effective electrical time constant of the horizontal cell membrane strongly depended on synaptic or voltage‐modulated conductances. 7. Satisfactory model simulations of all postsynaptic responses required that an e‐fold change in the release rate of transmitter from the rod be obtained with a 2 mV change in the rod potential.
Concentration of carbon dioxide, interstitial pH and synaptic transmission in hippocampal formation of the rat.
Authors: Balestrino M , Somjen G G
Published: December 2014

1. Interstitial pH (pHo) was measured with ion‐selective microelectrodes in the fascia dentata of rats anaesthetized with urethane, while CO2 levels were controlled by varying pulmonary ventilation and CO2 content of inspired air. In the CA1 sector of hippocampal tissue slices in vitro pHo was similarly measured and altered by varying CO2 in the gas phase, or by adding HCl or NaOH to the artificial cerebrospinal fluid (ACSF) of the bath, or by changing the concentration of HCO3‐. 2. Orthodromically evoked compound action potentials ('population spikes') were depressed in hypercapnia and increased in hypocapnia. In the fascia dentata of intact brains the population spike of the granule cells varied on average by more than 40% of control amplitude for each 0.1 change of pHo. In the CA1 zone of tissue slices in vitro, the change of population spike amplitude was approximately 30% per pH change of 0.1 caused by altered CO2 or HCO3‐ concentration, but only about 15% per pH change of 0.1 when HCl or NaOH were administered. 3. In anaesthetized rats the focal synaptic potential (FEPSP) evoked by a given stimulus intensity was weakly influenced by varying [CO2]; in tissue slices weak effects on FEPSP were inconsistent. In hippocampus both in situ and in vitro the population spike triggered by a given magnitude of FEPSP increased in hypocapnia and decreased in hypercapnia. This suggests that the main effect of CO2 is on the electric excitability of postsynaptic cells, with minor or no effect on transmitter release and on the interaction of the transmitter with its receptors. 4. Hypercapnia of anaesthetized rats was usually associated with a slight increase of [K+]o in the fascia dentata. Tissue [Ca2+]o changed little and not consistently. Neither of these two ions, nor concomitant changes of blood pressure or tissue partial pressure of oxygen, (Pt, O2), could account for the effects of pH on neuronal excitability. 5. The results show that increasing the extracellular concentration of H+ ions has a moderately depressant effect on the firing threshold of hippocampal neurones. The more powerful effects of elevated [CO2] and of lowered [HCO3‐] may probably be explained by a direct effect on the neuronal membrane. The brain, by regulating breathing, controls its own excitability.
Naloxone excites oxytocin neurones in the supraoptic nucleus of lactating rats after chronic morphine treatment.
Authors: Bicknell R J , Leng G , Lincoln D W , Russell J A
Published: December 2014

1. Lactating rats were implanted with a cannula in a lateral cerebral ventricle to deliver morphine (up to 50 micrograms/h) chronically from a subcutaneous osmotically driven mini‐pump. After infusion of morphine for 5 days the rats were anaesthetized with urethane and prepared with ventral surgery for recording the electrical activity of single, antidromically identified neurones in the supraoptic nucleus. 2. A single I.V. injection of naloxone (5 mg/kg) in these rats provoked a long‐lasting, large increase in intramammary pressure, but in control rats had negligible effects. Concentrations in plasma of oxytocin, measured by radioimmunoassay in samples of femoral arterial blood, rose from 44.7 +/‐ 2.5 to 1072.1 +/‐ 89.5 pg/ml (means +/‐ S.E.M.) 6 min after naloxone in the morphine‐treated rats. In control rats, the concentration of oxytocin in plasma rose only from 42.1 +/‐ 2.9 to 125.1 +/‐ 28.2 pg/ml after naloxone. 3. Naloxone produced a transient increase in arterial blood pressure in morphine‐treated but not control rats. Concentrations in plasma of vasopressin, measured by radioimmunoassay in samples of femoral arterial blood, rose in morphine‐treated rats from 7.4 +/‐ 2.4 to 29.2 +/‐ 3.7 pg/ml after naloxone, but did not rise significantly in control rats. 4. Naloxone (1‐5 mg/kg) produced a prompt and prolonged increase in the discharge rate of each of ten continuously active (putative oxytocin) cells recorded from ten morphine‐treated rats. The discharge rate of the six cells tested at the highest dose (5 mg/kg) increased by an average of 6.3 Hz (360%) within 5 min, and the firing rate remained elevated for at least 30 min; the discharge rate of six continuously active supraoptic neurones recorded in control rats was not affected by naloxone. 5. The firing activity of five phasic (putative vasopressin) supraoptic neurones in morphine‐treated rats was increased for at least 30 min by the injection of naloxone; these increases were the result of a raised intraburst firing rate with no change in burst duration or frequency. One phasic neurone was inhibited for 15 min, and one phasic neurone was unaffected. 6. The excitatory effects of naloxone on neurones in the supraoptic nucleus of morphine‐treated rats were not explained by changes in blood pressure or osmolarity and did not depend on suckling or a cholinergic pathway. 7. The concentrations of oxytocin in plasma and the operation of the milk‐ejection reflex were similar in the controls and morphine‐treated rats, prior to naloxone. These findings indicate tolerance to initial inhibitory effects of morphine on oxytocin secretion.(ABSTRACT TRUNCATED AT 400 WORDS)
Control of blood‐gas and acid‐base status during isometric exercise in humans.
Authors: Poole D C , Ward S A , Whipp B J
Published: December 2014

1. At a given level of pulmonary gas exchange, ventilation (VE) is appreciably higher during isometric exercise than during isotonic exercise. It is presently not clear whether the resultant hypocapnia represents a compensatory hyperventilation for an arterial metabolic acidaemia or whether it might reflect a primary respiratory alkalaemia. 2. To resolve this issue, five subjects performed isometric leg exercise designed to induce exhaustion in ca. 5 min and, on a separate occasion, ca. 8 min. VE, CO2 output (VCO2), O2 uptake (VO2) and end‐tidal gas tensions (PET,CO2, PET,O2) were measured breath‐by‐breath during exercise and recovery; arterialized venous blood (drawn from the dorsum of the heated hand) was sampled frequently and analysed for PCO2, PO2, pH, bicarbonate and lactate. These response profiles were compared with those resulting from exhausting bouts of isotonic leg exercise (cycle ergometry) of similar duration. 3. The isotonic exercise induced a metabolic (lactic) acidaemia with partial respiratory compensation. In contrast, isometric exercise consistently resulted in a respiratory alkalaemia, with little or no increase of blood [lactate]. At the end of the isometric exercise, VE fell abruptly and then rose again after a short interval (20 s, on average). This secondary stimulation presumably reflected the acid‐base consequences of the increased blood [lactate] (3‐5 mM, on average) which occurred in the recovery phase. 4. We therefore conclude that a primary respiratory alkalaemia occurs during isometric exercise, and that this results from ventilatory stimulation at a time when the 'exercise' metabolites are trapped within the contracting muscles as a consequence of impeded blood flow. The initial rapid reduction of ventilation which occurred at the cessation of the isometric exercise is consistent with a washing‐out of 'hyperpnoea‐inducing' metabolites from the muscles. Allowing for transit to the central circulation, the reduced ventilation is subsequently supplemented by a powerful humoral drive to breathe which results in a further hyperpnoea and secondary hypocapnia. Because of its latency, we hypothesize that this secondary hypocapnia is of peripheral chemoreceptor origin. 5. The ventilatory response profile for isometric exercise, and the subsequent recovery phase, supports the contention that both the exercising muscles and the peripheral chemoreceptors can be important sites for inducing hyperpnoea in humans.
Ionic basis of the differential neuronal activity of guinea‐pig septal nucleus studied in vitro.
Authors: Alvarez de Toledo G , López‐Barneo J
Published: December 2014

1. The electrical properties and ionic conductances of septal neurones were studied by intracellular recording in an in vitro slice preparation. Within the total number of cells recorded (n = 150) we identified three electrophysiological cell types, each one of them located in a separate septal region. Dorsolateral septal neurones comprised 60% of the cells, intermediate septal neurons 10%, and medical septal neurones 30%. 2. Passive electrical constants of dorsolateral, intermediate and medial septal neurones were, respectively:resting potential (‐60.2 +/‐ 4.8, ‐59.8 +/‐ 3.3 and ‐56 +/‐ 4.3 mV); input resistance (82.5 +/‐ 17, 63 +/‐ 16 and 83 +/‐ 18 M omega) and membrane time constant (18.5 +/‐ 7.3, 14.2 +/‐ 6.8 and 10.7 +/‐ 3.4 ms). 3. Direct activation of dorsolateral septal neurones by current injection below 0.2 nA triggered repetitive firing of fast action potentials. Larger current pulses elicited a characteristic response consisting of an initial fast action potential followed by a train of slow spikes. An after‐hyperpolarization followed termination of the pulse and the characteristic response. 4. In dorsolateral septal neurons tetrodotoxin (TTX) abolished the fast action potentials. The slow spikes and the after‐hyperpolarization disappeared in presence of Co2+ or after brief removal of external Ca2+. This suggests that the characteristic response is mediated by Ca2+ and the after‐hyperpolarization by a Ca2+‐dependent K+ conductance. 5. The firing pattern of intermediate septal neurones activated from the resting potential spontaneously measured in the cells was similar to that of dorsolateral septal neurones; but direct activation from a hyperpolarized membrane potential evoked in intermediate septal cells a bursting response due to the generation of a low‐threshold spike. The low‐threshold spike was TTX‐resistant but abolished by Co2+ and reached a maximal amplitude after hyperpolarization to ‐75 mV lasting for 100‐150 ms. These results suggest the existence in intermediate septal neurons of a low‐threshold Ca2+ conductance inactivated at the resting potential and deinactivated by hyperpolarization. 6. Depolarization of medial septal neurons by current pulses of amplitude greater than 0.2‐0.3 nA elicited a typical burst of two to six action potentials. The bursts lasted for 20‐50 ms and were followed by a marked after‐hyperpolarization.(ABSTRACT TRUNCATED AT 400 WORDS)
Cutaneous excitatory and inhibitory input to neurones of the postsynaptic dorsal column system in the cat.
Authors: Noble R , Riddell J S
Published: December 2014

1. In chloralose‐anaesthetized cats single‐unit microelectrode recordings were made from axons in the dorsal columns, at the lumbar level, identified as belonging to the postsynaptic dorsal column (PSDC) system. 2. Excitatory and inhibitory receptive field arrangements of a sample of seventy‐five PSDC neurones were examined in detail using natural cutaneous stimuli. 3. The sample was characterized by a high degree of convergent input: 80% of units were activated by both light tactile and noxious mechanical stimuli and more than half of those examined were excited by noxious radiant heat. In addition, three‐quarters of the units had inhibitory receptive fields on the ipsilateral limb. 4. Twenty‐three units (27%) were influenced by input from areas of both hairy and glabrous skin covering the foot and distal limb. Neurones in this group had complex receptive fields, many of which occupied several discontinuous areas of skin. Background and evoked activity of these units could frequently be inhibited by light tactile and/or noxious stimuli. Their inhibitory receptive fields occupied small areas of skin overlapping or adjacent to excitatory fields. 5. Fifty‐two units (73%) had receptive fields restricted to areas of hairy skin on the thigh and upper hindlimb. Half the units in this group had coextensive low‐ and high‐threshold excitatory areas but about one‐third had a concentric receptive field organization; a high‐threshold excitatory component extending beyond, or around, a central low‐threshold area. The discharge of these units could be inhibited only by light tactile stimuli. Their inhibitory receptive fields covered extensive areas of skin, sometimes completely surrounding the excitatory field. 6. The complex receptive field arrangements observed for neurones of the postsynaptic dorsal column system are discussed in relation to previous observations on dorsal horn neurones of other ascending tracts.
Somatosensory projections to the superior colliculus of the anaesthetized cat.
Authors: Abrahams V C , Clinton R J , Downey D
Published: December 2014

1. Experiments in anaesthetized cats have shown that the superior colliculus receives deep afferent input from the forelimb and hindlimb, but not from the large superficial neck muscles. 2. Neuronal activity in the superior colliculus is readily elicited by electrical stimulation of C2 and C3 cutaneous nerves. A significant proportion of neurones so activated have multiple receptive fields and some with no identifiable receptive fields in regions innervated by C2 and C3 nerves have receptive fields elsewhere on the body surface. Many collicular neurones activated by C2 and C3 stimulation had no identifiable receptive fields. 3. Natural stimuli to the limbs, hitherto believed to activate only cutaneous receptors, are sufficient to activate deep receptors which contribute to the neuronal responses in the superior colliculus elicited by the natural stimulus. These same natural stimuli set up transmitted vibration adequate to excite receptors some distance from the applied stimulus. 4. No evidence was found for a rigorous somatotopy in the superior colliculus. The great majority of neurones received trigeminal input which is widely distributed throughout the superior colliculus. 5. Tactile stimuli to the face are most effective in eliciting unit activity in the superior colliculus and many neurones activated by these stimuli were shown to be tectospinal neurones. In particular, the specialized receptors of the face, including the glabrous skin of the snout (the planum nasale) and the vibrissae, are major sources of input to collicular neurones including tectospinal neurones. 6. It is suggested that a major role of the superior colliculus is in the organization of head movements associated with the use of the specialized receptor organs of the face in exploratory behaviours. The superior colliculus may also be involved in the organization of aversion movements of the head.
Presynaptic P1‐purinoceptors in jejunal branches of the rabbit mesenteric artery and their possible function.
Authors: Illes P , Jackisch R , Regenold J T
Published: December 2014

1. Excitatory junction potentials (EJPs) evoked by nerve stimulation with fifteen pulses at 1 Hz were recorded from smooth muscle cells of the rabbit isolated mesenteric artery. The effects of P1‐purinoceptor agonists and antagonists, as well as of substances which interfere with the inactivation of endogenous adenosine, were tested. 2. Adenosine and its analogues depressed the EJPs in the train in a concentration‐dependent manner. The percentage inhibition of the first EJP and that of the later ones was similar; some early EJPs, however, were inhibited more markedly. The rank order of potency of the agonists was (‐)‐N6‐(R‐phenylisopropyl)‐adenosine (R‐PIA) congruent to 5'‐N‐ethylcarboxamidoadenosine (NECA) greater than (+)‐N6‐(S‐phenylisopropyl)‐adenosine (S‐PIA) greater than adenosine. The respective IC40 values (the concentrations producing 40% inhibition of the first EJP in the train) were 0.018, 0.028, 0.83 and 4.7 mumol/l. 3. Three methylxanthines, namely 8‐phenyltheophylline (1, 10 mumol/l), 8‐cyclopentyltheophylline (0.1, 1 mumol/l) and 8‐(p‐sulphophenyl)‐theophylline (100 mumol/l), antagonized the effect of R‐PIA (0.1 mumol/l). When given alone they also enhanced the amplitudes of all EJPs in the train. The percentage facilitation of the first EJP and that of the later ones was similar. Some early EJPs, however, were potentiated more markedly. 8‐Phenyltheophylline was less potent than 8‐cyclopentyltheophylline both in preventing the action of R‐PIA and in enhancing the EJPs. A concentration (100 mumol/l) of 8‐(p‐sulphophenyl)‐theophylline, which strongly antagonized the R‐PIA effect, produced only a moderate facilitation of EJPs. 4. S‐(p‐nitrobenzyl)‐6‐thioguanosine (10 mumol/l) both depressed the EJPs, and enhanced the inhibitory effect of adenosine. Adenosine deaminase (10 micrograms/ml) caused some potentiation of EJPs; this action was prevented by a concentration (10 mumol/l) of deoxycoformycin, which had no effect of its own. AH21‐132 (10 mumol/l) enhanced all EJPs in the train. 5. None of the above substances influenced the resting membrane potential of the smooth muscle cells. In addition, R‐PIA (0.1 mumol/l) did not change the depolarization induced by noradrenaline (3 mumol/l). 6. We suggest that the axon terminals of postganglionic sympathetic neurones in the rabbit mesenteric artery possess P1‐purinoceptors of the A1‐type. The activation of these presynaptic receptors by endogenous adenosine may inhibit the release of the main neuroeffector transmitter, which is probably ATP.(ABSTRACT TRUNCATED AT 400 WORDS)
The effect of temperature on neuromuscular transmission in the main caudal artery of the rat.
Authors: Cassell J F , McLachlan E M , Sittiracha T
Published: December 2014

1. Excitatory junction potentials (EJPs) recorded in isolated segments of the proximal main ventral artery of the rat tail were reduced in amplitude and prolonged in time course as temperature was lowered from 35 to 15 degrees C. 2. The slow depolarization that followed the EJPs after supramaximal or repetitive perivascular stimulation was markedly slowed in time course, but little affected in amplitude, as temperature was lowered. 3. The time constant (tau EJP) of the exponential decay phase of the EJP recorded from cells deep in the media was similar to the membrane time constant, so that the increase in tau EJP at low temperatures is consistent with a decrease in membrane conductance. 4. The value of tau EJP was also prolonged if the EJP was evoked at the time of the peak of the slow depolarization; this effect was blocked by idazoxan (10(‐7) M) but not by prazosin (10(‐6) M). 5. During repeated short bursts of high‐frequency stimulation, action potential initiation was facilitated by both the prolongation of EJPs and summation of slow depolarizations; these effects were greater at 25 than at 35 degrees C. 6. The interactions between EJPs and alpha‐adrenoreceptor‐mediated membrane conductance changes are considered with respect to the electrical events occurring during sympathetic neuromuscular transmission at the natural temperatures of the rat tail.
Information processed by dorsal horn spinocerebellar tract neurones in the cat.
Authors: Edgley S A , Jankowska E
Published: December 2014

1. A group of spinocerebellar tract neurones located in the dorsal horn of the mid‐lumbar segments of the spinal cord but outside of Clarke's column have been investigated by intracellular and extracellular recording from their somata. The existence of these neurones has been demonstrated previously using anatomical methods, but their properties have not been investigated in detail. In contrast to the cells of Clarke's column, these neurones were found to process information from both exteroceptors and proprioceptors. 2. All of the investigated neurones were powerfully excited following stimulation of muscle nerves at strengths sufficient to activate group II afferents while there was no evidence for actions from group I afferents onto any of them. Most were excited by group II afferents from many different nerves, including those from muscles acting on different joints. The latencies and properties of the excitatory postsynaptic potentials (EPSPs) suggest that at least a large proportion of them were monosynaptically evoked. 3. All of the neurones were powerfully excited following electrical stimulation of cutaneous afferents. The most potent effects were evoked from the saphenous and sural nerves which innervate the skin of the leg and thigh. In many cases these EPSPs had latencies indicative of a monosynaptic connection. The superficial peroneal and tibial nerves which innervate the skin of the foot evoked EPSPs which were usually smaller and of longer latency. 4. Responses to adequate stimulation of cutaneous afferents were examined in twenty extracellularly recorded neurones. All but one of them could be discharged by weak mechanical stimulation of the skin over the proximal part of the leg and thigh. None were activated from the skin of the foot. 5. Some of the neurones were influenced by stimulation of the posterior knee joint or interosseous nerves. These actions were relatively weak, however, suggesting that the powerful effects seen on stimulation of muscle nerves were unlikely to have been mediated by articular or Pacinian afferents which contaminate them. 6. Excitation from group II afferents was sometimes followed by inhibition (in 27% of the neurones). In almost all cases the inhibitory postsynaptic potentials (IPSPs) were evoked from the same nerves which evoked EPSPs. The minimal latencies of the IPSPs were approximately 1.0 ms longer than those of the EPSPs, suggesting that they were evoked disynaptically. 7. The possibility that these neurones provide information regarding limb position is discussed.
Ventromedial hypothalamus is highly sensitive to prostaglandin E2 for producing fever in rabbits.
Authors: Morimoto A , Murakami N , Nakamori T , Watanabe T
Published: December 2014

1. The febrile responses induced by intraventricular or intrapreoptic (bilateral) injections of prostaglandin E2 (PGE2) were investigated in the same group of rabbits. Both injections produced dose‐dependent fever over a range of 100‐2000 ng. However the magnitude of febrile responses induced by ventricular injections was significantly greater than those by intrapreoptic injections. This indicates that there exist regions more sensitive to PGE2 than the preoptic region for producing fever. 2. To explore the regions sensitive to PGE2, the effects of microinjection (1 microliter) of PGE2 (50 and 100 ng) on the rectal temperature were extensively examined in the forty regions of the brain stem. The results showed that the preoptic and anterior hypothalamic region, and the ventromedial hypothalamic region are highly sensitive to PGE2 for producing fever. 3. The febrile responses to PGE2 (50‐1000 ng) microinjected into the preoptic region were compared with those induced by injection in the ventromedial hypothalamic region. Fever induced by injection in the ventromedial hypothalamic region was significantly greater than that by injection into the preoptic region. 4. Fever induced by PGE2 injected into the ventromedial hypothalamic region was due to increased heat production in the cold environment (10 degrees C), while in 24 degrees C environment heat losses were reduced without significant changes in heat production. 5. The present results show that the ventromedial hypothalamic region is the most sensitive region to PGE2 for producing fever.
Modification of renal and tissue cation transport by cholecystokinin octapeptide in the rabbit.
Authors: Duggan K A , Hams G , MacDonald G J
Published: December 2014

1. Reports that gastric sodium loads cause a greater natriuresis than those administered intravenously, suggest that a gastric or portal sodium monitor exists which releases a humoral natriuretic factor. To determine whether cholecystokinin octapeptide (CCK‐8) had direct renal natriuretic effects (and was therefore a candidate for this gut‐derived natriuretic factor) we compared the natriuretic response to CCK‐8 infused intravenously with that infused directly into the renal artery of six conscious male rabbits. 2. CCK‐8 produced a significant log dose‐dependent decrease in the fractional excretions of calcium (P less than 0.05) and magnesium (P less than 0.005) and a log dose‐dependent increase in fractional sodium excretion (P less than 0.025). The significant decreases in the fractional excretions of calcium and magnesium were accompanied by log dose‐dependent falls in their plasma levels (calcium, P less than 0.05, and magnesium, P less than 0.005), indicating movement of calcium and magnesium to extravascular sites. Studies of tissue calcium and magnesium levels in response to CCK‐8 infusion showed that calcium accumulated in kidney and skeletal muscle. 3. We conclude that CCK‐8 has direct renal natriuretic effects at the tubular level and could be the gut‐derived natriuretic factor. In addition to its effects on sodium excretion, CCK‐8 causes renal retention and increased gut absorption of calcium and magnesium with movement of these ions to extravascular sites.
Heat production of quiescent ventricular trabeculae isolated from guinea‐pig heart.
Authors: Daut J , Elzinga G
Published: December 2014

1. A new calorimetric technique has been developed which allows continuous measurement of the rate of energy expenditure in superfused preparations of cardiac muscle. Thin trabeculae of guinea‐pig ventricular muscle were mounted in a Perspex tube of 0.8 mm inner diameter and the temperature difference of the perfusate upstream and downstream of the preparation was measured. 2. The resting heat rate of trabeculae of 240‐575 microns diameter from guinea‐pig heart was determined repeatedly for up to 6 h after cardiectomy. It did not vary with time during the course of the experiment. 3. The average resting heat rate measured in HEPES‐buffered Tyrode solution containing 20 mM‐glucose and 2 mM‐pyruvate as substrates was 130 +/‐ 29 mW/g dry weight or 36 +/‐ 8 mW/cm3 of tissue (n = 15). This is an order of magnitude larger than the resting heat rate reported in the literature for isolated cardiac preparations. 4. After omitting the pyruvate from the superfusate the resting heat rate decreased to 60‐70% of its steady value within 4 min. After readmission of pyruvate this effect was reversed. The average resting heat rate with glucose as sole substrate was 23 +/‐ 4 mW/cm3. 5. Uncoupling of the mitochondria by 50 microM‐2,4‐dinitrophenol (DNP) increased the heat rate up to 170 mW/cm3. This effect could be maintained for several minutes and was fully reversible. Raising the external K+ concentration to 150 mM (NaCl replaced by KCl) induced a transient rise in the rate of heat production up to 115 mW/cm3. 6. The heat production during uncoupling of the mitochondria and during potassium contractures was inversely related to the diameter of the preparation. Calculation based on Hill's equation (Hill, 1928) indicated that this was caused by the development of anoxia at the core of the preparation. 7. In contrast, the rate of heat production of quiescent preparations was not correlated with diameter and calculation indicated that at rest there was no anoxic core. The high value of resting heat rate found in the present study is discussed within the context of the large variation of 1.7‐25 mW/g reported in the literature for resting metabolic rate of cardiac muscle.
Sympathetic activation of lipid synthesis in brown adipose tissue in the rat.
Authors: Minokoshi Y , Saito M , Shimazu T
Published: December 2014

1. The roles of the sympathetic nerves in regulating lipid synthesis in brown adipose tissue (BAT) were studied by measuring incorporation of 3H from 3H2O into glyceride glycerol and glyceride fatty acids in the interscapular BAT in anaesthetized rats. 2. When noradrenaline was infused intravenously at a total dose of 1‐8 micrograms/100 g body weight over 30 min, 3H incorporation into glyceride glycerol increased whereas 3H incorporation into fatty acids did not change. Similar responses were found when the sympathetic nerves entering the interscapular BAT were stimulated continuously at 10 Hz. However, when electrical stimuli consisting of a much shorter train (2 s) were applied to the nerves at 3 min intervals at 10 Hz (stimulation in bursts). 3H incorporation into both glyceride glycerol and fatty acids was enhanced. Stimulation in bursts elicited more pronounced lipogenic responses than other patterns that were employed, and involved the delivery of precisely the same number of impulses over the whole period of stimulation. The lipogenic responses to nerve stimulation in bursts were increased by increasing the stimulus frequency over the range 4‐40 Hz. 3. Simultaneous administration of propranolol and phenoxybenzamine had little effect on either the fatty acid or the glyceride glycerol response to nerve stimulation. In contrast, these blocking agents almost completely eliminated the responses to noradrenaline infusion. 4. Pre‐treatment with guanethidine effectively abolished the lipogenic response to nerve stimulation but potentiated the response to noradrenaline infusion. 5. It is concluded that lipid synthesis in BAT is enhanced by direct electrical stimulation of the sympathetic nerves only when they are stimulated in bursts. Sympathetic activation of lipogenesis in BAT is not solely attributable to the action of noradrenaline but involves some non‐adrenergic mechanism.
Development of sodium and chloride transport across fetal and newborn rat stomach in vitro.
Authors: Ducroc R , Garzon B , Geloso J P , Hervatin F , Millet P , Moreau E
Published: December 2014

1. Unidirectional and net Na+ and Cl‐ fluxes were determined across isolated fetal rat stomach 19‐21 days post‐coitum, and across the stomach of newborn rats aged 5 or 12 days. 2. On fetal day 19, absorption of both Na+ and Cl‐ was greater than the short‐circuit current, Isc (net Na+ flux, JnetNa = 4.7 +/‐ 1.0 and net Cl‐ flux, JnetCl = 5.4 +/‐ 1.4 mu equiv cm‐2 h‐1 vs. Isc = 0.9 +/‐ 0.1 mu equiv cm‐2 h‐1). Mucosal addition of 10 microM‐amiloride did not significantly alter JnetNa, JnetCl, Isc or total conductance. 3. However, on fetal day 20, neutral absorption of NaCl was no longer observed but amiloride had inhibited electrogenic absorption of Na+, and significant active secretion of Cl‐ was observed (JnetCl = ‐1.3 +/‐ 0.6 mu equiv cm‐2 h‐1). On day 21 (i.e. 24 h before birth), values for JnetNa, JnetCl, and Isc were not different from those determined on adult gastric mucosa. 4. After birth, NaCl transport continued to exhibit its prenatal characteristics on day 5 but not on day 12, when Na+ and Cl‐ were both absorbed; on that day, JnetNa‐Isc was equal to both JnetCl and to the amiloride‐insensitive component of Isc, indicating that neutral NaCl absorption had resumed. 5. These data show that in rat stomach, NaCl transport differentiates on fetal day 20, when H+ secretion is first observed, and thereafter undergoes biphasic development. 6. The significant Cl‐ absorption observed on post‐natal day 12 was concomitant with the inhibition of net H+ secretion.
Cardiovascular changes associated with augmented breaths in normoxia and hypoxia in the rat.
Authors: Marshall J M , Metcalfe J D
Published: December 2014

1. In the present study, anaesthetized rats showed respiratory gasps (augmented breaths) at regular intervals during air breathing and at increased frequency during hypoxia (breathing 15, 12, 8 or 6% O2 in N2). Each augmented breath was accompanied by transient vasodilatation in hindlimb skeletal muscle and sometimes bradycardia. In hypoxia these changes were superimposed upon more gradual muscle vasodilatation and tachycardia. 2. Both the augmented breaths and the transient muscle vasodilatations disappeared immediately after bilateral vagotomy but both sometimes reappeared 1‐2 h later, particularly in hypoxia. 3. The transient vasodilatation in skeletal muscle sometimes preceded the augmented breath, indicating that the vasodilatation was not a reflex initiated by pulmonary stretch receptors secondary to the augmented breath. Moreover, hyperinflation of the lungs to 5‐10 mmHg evoked the Breuer‐Hering respiratory reflex but had no effect upon the cardiovascular variables. 4. Addition of SO2 (300‐400 p.pm.) to the inspirate, which others have shown preferentially blocks pulmonary stretch receptors, abolished the Breuer‐Hering reflex, but had no significant effect on baseline levels of muscle vascular conductance or heart rate during normoxia, nor on the gradual increases in these variables during hypoxia (8% O2). Moreover, augmented breaths still occurred during air breathing and during hypoxia, each being associated with transient muscle vasodilatation. 5. These results indicate that pulmonary stretch receptors have little reflex effect upon the cardiovascular system of the rat either in normoxia or hypoxia. Rather, we suggest that transient muscle vasodilatation and possibly bradycardia, as well as an augmented breath, are all part of a primary reflex, initiated by pulmonary irritant receptors, and facilitated by peripheral chemoreceptor stimulation, repetition of which is an integral part of the response to hypoxia.
Direct observations of the effects of baroreceptor stimulation on skeletal muscle circulation of the rat.
Authors: Hébert M T , Marshall J M
Published: December 2014

1. In anaesthetized rats, supramaximal baroreceptor stimulation by carotid sinus inflation evoked a reflex fall in arterial pressure and an increase in vascular conductance and flow of muscles of the hindquarters. 2. Simultaneously, main arteries, primary and secondary arterioles (13‐90 microns, internal diameter (i.d.)) and terminal arterioles (7‐13 microns) of the spinotrapezius muscle all showed a diameter increase that reached a peak as arterial pressure neared its zenith; terminal arterioles then showed a diameter decrease to below control level. These responses were abolished by local application of phentolamine or guanethidine to the spinotrapezius, or by crushing the paravascular nerve supply. 3. It is suggested that the diameter increases were mediated by reflex inhibition of sympathetic tone, while the secondary diameter decrease in terminal arterioles was induced by a fall in local concentrations of vasodilator metabolites, caused by an increase in muscle blood flow. 4. But after sympathetic blockade 25% of all arterial vessels showed a diameter increase beginning as the fall in arterial pressure neared its zenith. These responses may be attributed to vasodilator metabolites accumulating as a consequence of a reduction in muscle blood flow secondary to the reflex reduction in perfusion pressure. 5. No venous vessels, from venules (9‐18 microns) to main veins (65‐130 microns) that drain the muscle, showed a diameter change in response to baroreceptor stimulation, in accord with evidence that they have no sympathetic supply. 6. These results accord with and can provide explanation for changes in blood flow, regional blood volume and capillary filtration evoked by baroreceptor stimulation in studies on whole‐limb muscle. They support suggestions that active changes in capacity of venous vessels of muscle play a minor role in the baroreceptor reflex; both active and passive changes in vascular capacity may be due to large veins outside of muscle proper.
Thermosensitivity of the goat's brain.
Authors: Heath M E , Jessen C
Published: December 2014

1. Experiments were done in conscious goats to estimate the gain of brain temperature sensors and to evaluate that fraction of the thermosensitivity of the entire brain which can be determined by a thermode located in the hypothalamus. 2. The animals were implanted with local thermodes, carotid loops and intravascular heat exchangers permitting independent control of hypothalamic temperature, extrahypothalamic brain temperature and trunk core temperature. 3. Small and slow ramp‐like displacements of hypothalamic temperature generated continuously increasing thermoregulatory responses without any dead band, if a negative feed‐back from extrahypothalamic sources was suppressed. 4. The hypothalamic sensitivity determined by the metabolic response to slow ramp‐like cooling of the thermode amounted to ‐1.4 W/(kg degrees C) and equalled approximately 30% of what had been found for total body core sensitivity in another series of experiments. 5. Total brain thermosensitivity was ‐1.6 W/(kg degrees C), which implies that a large thermode centred in the hypothalamus can detect approximately 85% of the thermosensitivity of the entire brain.
Stretch sensitization of human muscle spindles.
Authors: Edin B B , Vallbo A B
Published: December 2014

1. Sixty‐seven afferents from the finger extensor muscles were consecutively recorded by microneurography. 2. The units were classified as primary or secondary muscle spindle afferents or Golgi tendon organ afferents on the basis of their responses to ramp‐and‐hold stretches, sinusoidals superimposed on ramp‐and‐hold stretches, maximal twitch contractions and isometric contractions and relaxations. 3. The muscle was repeatedly stretched and then either kept short or long for a few seconds followed by a slow ramp stretch. The responses of the muscle afferents to the slow stretch were compared under the two conditions. 4. Thirty out of thirty‐eight units classified as primary spindle afferents and four out of eleven units classified as secondary afferents showed an enhanced response to the slow ramp when the muscle had been kept short compared to the response when the muscle had been kept long. 5. None of the eighteen Golgi tendon organ afferents showed any difference in this respect. 6. It is concluded that stretch sensitization does occur in human muscle spindles and, when present, constitutes firm evidence of the afferent originating from a muscle spindle rather than a Golgi tendon organ. In addition, due to differences in the response characteristics of primaries and secondaries, the test may aid in separating muscle spindle primary afferents from secondary afferents.
Arrhythmogenic interaction between low potassium and ouabain in isolated guinea‐pig ventricular myocytes.
Authors: Aronson R S , Nordin C
Published: December 2014

1. The two‐microelectrode method of voltage clamp was used in single myocytes isolated from guinea‐pig ventricles to investigate the mechanism underlying the arrhythmogenic interaction between low external K+ and digitalis. 2. We investigated the effects of ouabain (10(‐6) M) with 4 mM‐K+ or 2 mM‐K+ on the peak magnitude of the inward component of oscillatory current (Iti) recorded upon repolarization to the resting potential after depolarizing clamps to ‐5 mV, and on the characteristics of the steady‐state current‐voltage relationship. 3. Whereas ouabain with 4 mM‐K+ did not alter the current‐voltage relationship from its control shape, ouabain with 2 mM‐K+ caused marked changes in the curve: the zero‐current intercept was shifted in a negative direction, the region of low slope conductance was extended to more negative potentials, and the curve was shifted downward relative to the control current‐voltage relationship. The changes in the current‐voltage relationship induced by ouabain with 2 mM‐K+ were very similar to those induced by 2 mM‐K+ alone. 4. The functional consequence of the changes in the current‐voltage relationship induced by ouabain with 2 mM‐K+ was a highly significant reduction in the amount of outward current (Ith) needed to reach the threshold for excitation; Ith was reduced from 1.6 +/‐ 0.4 nA (n = 6) in ouabain with 4 mM‐K+ to 0.8 +/‐ 0.3 nA (n = 5) in ouabain with 2 mM‐K+. 5. The mean value for Iti was larger in ouabain with 2 mM‐K+ (0.58 +/‐ 0.41 nA, mean +/‐ S.D., n = 4) than in ouabain with 4 mM‐K+ (0.42 +/‐ 0.38 nA, n = 5). Although the increase in Iti was not statistically significant because of the large variability of the measurement, it is possible that the increase might be physiologically significant. 6. Our results suggest that the arrhythmogenic interaction between digitalis and low K+ is due to the combined effects of low K+ on the current‐voltage relationship and on the size of the peak inward current induced by ouabain. Whereas the effect of low K+ and ouabain on the inward current was highly variable, the effects on the current‐voltage curve were far more consistent, pointing to an important role for alterations in the current‐voltage relationship in the arrhythmogenic interaction between low K+ and ouabain.
Membrane properties of nociceptive neurones in lamina II of lumbar spinal cord in the cat.
Authors: Iggo A , Molony V , Steedman W M
Published: December 2014

1. Intracellular recordings were made from neurones in lamina II of the dorsal horn of the lumbar spinal cord of the cat, and the electrotonic responses to brief rectangular current pulses of up to 0.5 nA passed through the recording microelectrode measured. 2. The majority of penetrations were associated with input resistances lower than 70 M omega, low resting potentials (‐25 to ‐45 mV) and frequent firing of action potentials. Stable resting potentials of ‐50 to ‐75 mV were recorded in twenty neurones which exhibited continuous ongoing synaptic activity without action potentials. The threshold for action potential initiation was around ‐42 mV. The current‐voltage relationships were linear over most of the range of currents used; with depolarizing currents rectification became apparent close to the firing threshold. Input resistances ranged from 80 to 150 M omega. 3. The time course of the decay of the electrotonic response was exponential with a time constant of 0.8‐2.0 ms. The morphology of the cells‐‐small soma with a small number of fine processes‐‐and these short time constants suggest that axial current flow is limited and that the charge is dissipated locally within the soma through the membrane capacitance. 4. Effective membrane capacities were calculated from the estimated soma surface area of typical neurones in lamina II stained with HRP, and assuming a specific membrane conductance of 1.0 microF cm‐2 they ranged from 3.1 to 15.7 pF. Membrane capacities were calculated for the twenty neurones in this study from measurement of input resistance and time constants (6.4‐15.0 pF) and lay within this range. 5. Three neurones which had their electrical properties measured were also stained with horseradish peroxidase (HRP). Their specific membrane capacitances (1.1‐1.2 microF cm‐2) and specific resistances (0.9‐1.1 k omega cm2) were within the range of values measured for other neurones in the CNS. 6. The short time constants found for these neurones suggests that temporal summation of postsynaptic potentials evoked by short‐acting neurotransmitters will be limited. This may help to explain why action potentials arise singly from discrete, short‐lived EPSPs. There is anatomical evidence for multiple connections from terminal branches of A delta and C afferent fibres within the superficial dorsal horn; this suggests that spatial summation of EPSPs is a major factor in synaptic integration of some of the primary afferent inputs to these neurones.
Effects of pilocarpine on breathing movements in normal, chemodenervated and brain stem‐transected fetal sheep.
Authors: Hanson M A , Moore P J , Nijhuis J G , Parkes M J
Published: December 2014

1. We examined the effects on fetal breathing movements (FBM) and electrocortical activity (ECoG) of the administration of pilocarpine to three groups of fetal sheep in utero: one group had peripheral chemodenervation; one group had peripheral chemodenervation and transection of the brain stem at the level of the colliculi; a third group of sham‐operated animals acted as a control. 2. Pilocarpine induced a period of FBM characterized by their high amplitude (ca. 24 mmHg) and low frequency (ca. 0.65 Hz). It also produced low‐voltage ECoG. These effects were seen both in normoxia and in hypoxia. They were independent of the ECoG state in which the drug was given. 3. In normoxia, pilocarpine‐induced FBM were blocked by cholinergic antagonists which enter the central nervous system, atropine sulphate and scopolamine hydrobromide, but were either unaffected or were reduced in amplitude by antagonists with restricted access to the central nervous system, atropine methylnitrate and scopolamine methylbromide. In hypoxia, atropine sulphate and scopolamine hydrobromide again blocked FBM but now scopolamine methylbromide and atropine methylnitrate blocked the FBM in 42% of trials. In the remaining trials FBM remained virtually unchanged. 4. No differences were observed in the effects of pilocarpine on FBM or ECoG between chemodenervated fetuses and those which had been sham‐operated. 5. In fetuses with transection of the brain stem, breathing was continuous irrespective of the ECoG. Pilocarpine increased the amplitude of FBM but did not alter the frequency of these FBM. These effects occurred both in normoxia and in hypoxia. 6. We conclude that pilocarpine produces effects on fetal behaviour via at least two sites in the central nervous system. One site lies in the pons or medulla and is responsible for the stimulation of FBM. The other site is above the level of the colliculi and is responsible for producing sustained low‐voltage ECoG. These effects do not require the integrity of the peripheral chemoreceptors and we find no evidence to support the previous suggestion that the action of pilocarpine is via stimulation of these receptors.