bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of peripheral nerve lesions and of neonatal capsaicin in the rat on primary afferent depolarization
Authors: Wall Patrick D. 
Published: December 2014

1. In anaesthetized adult rats with intact peripheral nerves, a conditioning orthodromic volley in myelinated afferents produces a prolonged increase in the excitability of the terminals of the afferents which have carried the orthodromic volley and in the terminals of their passive neighbours. This phenomenon, primary afferent depolarization, p.a.d., is shown by the antidromic stimulation of afferents with a micro‐electrode in the dorsal horn and by recording the antidromic volley on a cut peripheral nerve.2. If a peripheral nerve is cut and ligated, the size of the myelinated afferent volley generated by stimulation proximal to the cut and measured on dorsal roots is not affected for 14 days after the cut (Wall & Devor, 1981). Similarly the size of the volleys ascending the cord in axons from cord cells remains unaffected.3. If a peripheral nerve is cut and tested after 7‐14 days, it produces a markedly decreased p.a.d. on itself and on its neighbours.4. If a nerve is crushed rather than cut, it produces a normal p.a.d. on itself and its neighbours after 7‐14 days.5. In animals treated neonatally with capsaicin, there is a severe loss of unmyelinated afferents. Testing the effect of an orthodromic volley in myelinated afferents on the excitability of myelinated afferent central terminals shows that there is a strongly decreased p.a.d. in these animals.6. It is concluded that primary afferent depolarization is sensitive to peripheral nerve lesions and that it may be particularly dependent on the integrity of the unmyelinated afferents in spite of the fact that p.a.d. is measured as a phenomenon of myelinated afferents acting on myelinated afferents.
Altered developmental changes of neuromuscular junction in hypo‐ and hyperthyroid rats
Authors: Kawa Kazuyoshi , Obata Kunihiko 
Published: December 2014

1. Effects of thyroid hormone on the development of neuromuscular junctions (n.m.j.s.) were investigated electrophysiologically in the diaphragms (sternal region) of normal, hypo‐ and hyperthyroid rats from the age of birth (day 0) to day 35.2. Hypothyroidism in new‐born rats was induced either by daily administration of propylthiouracil to mothers or by subcutaneous injection of 150 μCi 131I on day 1. Hyperthyroidism was induced by daily injection of thyroxine.3. In normal rats up to day 10, muscle fibres were innervated polyneuronally. By day 20, multiple innervation was eliminated and muscle fibres received only a single input. In hypothyroid rats elimination of polyneuronal innervation was retarded by 5‐8 days, while in hyperthyroid rats the elimination was accelerated by 2‐3 days.4. The frequency of miniature end‐plate potentials (m.e.p.p.s) in normal rats increased from one per 40 sec on days 0‐5 to 1/sec on days 25‐35. The m.e.p.p. frequency in hypothyroid rats was 25‐65% of that in normal rats of the same age. In hyperthyroid rats the m.e.p.p. frequency was normal up to day 18 but subnormal afterwards. The duration of m.e.p.p. measured on day 22‐23 was slower in hypothyroid rats and faster in hyperthyroid rats, relative to m.e.p.ps in normal rats.5. The sensitivity to acetylcholine (ACh) at extrajunctional regions in normal rats was about 100 mV/nC at birth and declined to 1 mV/nC by day 26. In hypothyroid rats, the ACh sensitivity was as high as 30 mV/nC on day 26; in hyperthyroid rats, ACh sensitivity on day 26 was undetectable.6. With pairs of nerve stimuli (applied at a 50 msec interval), the second end‐plate potential was facilitated until day 10 and depressed after day 16 in normal rats. This shift from facilitation to depression during development was not altered in either hypo‐or hyperthyroid rats.7. It is concluded that the lack and excess of thyroid hormone retards and facilitates the development of n.m.j.s. respectively. Possible mechanisms for this altered development are discussed.
The calcium‐activated potassium conductance in guinea‐pig myenteric neurones
Authors: Morita K. , North R. A. , Tokimasa T. 
Published: December 2014

1. Intracellular recordings were made from guinea‐pig myenteric neurones in vitro.2. From one to sixty action potentials were followed by an afterhyperpolarization, the amplitude and duration of which increased with the number of preceding action potentials.3. The afterhyperpolarization reversed its polarity at a membrane potential of ‐91 mV. This value changed by 58 mV when the potassium concentration of the perfusing solution was changed ten‐fold.4. The afterhyperpolarization was abolished in calcium‐free solutions. It was shortened in low calcium (1·2 mM) solutions and prolonged in solutions which contained high (5·0 mM) calcium concentrations, TEA (1 mM) or caffeine (1 μM).5. The conductance increase during the afterhyperpolarization (gK, Ca) was calculated from the amplitude of electrotonic potentials, taking advantage of the lack of membrane rectification in the range ‐60 to ‐90 mV. Peak gK, Ca increased as the number of action potentials was increased, but was relatively independent of membrane potential in this range.6. gK, Ca declined with a time course which was single exponential (time constant 1·5‐5 s) following one to six action potentials, and double exponential (time constants about 3 and 12 s) following fifteen to sixty action potentials.7. It is concluded that the calcium which enters the neurone during the action potential elevates the membrane potassium conductance. The time course of this conductance increase probably reflects the free intracellular calcium concentration, and therefore describes the calcium sequestration or extrusion process.
Block and activation of the pace‐maker channel in calf Purkinje fibres: effects of potassium, caesium and rubidium
Authors: DiFrancesco Dario 
Published: December 2014

1. The effects of low concentrations of Cs+ (0·01‐3mM) on the fully activated I-V relation īf(E) for the pace‐maker current in calf Purkinje fibres have been investigated. The action of Cs+ is two‐fold: in the negative region of the I-V curve Cs+ induces a channel blockade; on the other hand, at more positive potentials Cs+ can produce the opposite effect, i.e. a current increase.2. Cs+‐induced blockade is concentration‐ and voltage‐dependent, as observed on other cation channels. Data in the far negative voltage range (about ‐ 150 to ‐ 50 mV) can be fitted by a simple block model (Woodhull, 1973), which gives a mean value of 0·71 for the fraction of membrane thickness (δ) crossed by Cs+ ions before reaching the blocking site. The value of δ does not appear to be affected by either external Na or external K concentrations. Values for the dissociation constant of the blocking reaction at E = 0 mV (k0) are found in the range 0·5‐3·7 mM. In the positive region of the īf(E) relation the current depression caused by channel blockade vanishes. Unexpectedly, in this range the current can be observed to increase with Cs+, and īf(E) curves in different Cs+ concentrations show cross‐over.3. Changing external K+ also produces similar cross‐over phenomena. Investigation of this effect reveals that the increase in slope of the I-V curve on raising the external K+ concentration follows Michaelis—Menten kinetics, and can be interpteted in terms of K+‐induced channel activation. It is found that 44±6 mM‐K+ half‐saturates the channel activating reaction.4. The Cs+‐induced current increase is large in low‐K+ solutions and vanishes in high‐K+ solutions, suggesting a competition between Cs+ and K+ ions in their activating action. Increasing Na+ also limits the Cs+‐induced current increase.5. Rb+ also blocks the if channel, though less efficiently than Cs+. The block caused by Rb+ is, unlike that of Cs+, nearly voltage‐independent, and is explained by assuming that the blocking reaction occurs near the external mouth of the channel (mean value of δ is 0·05). The zero‐voltage dissociation constant (k0) of the Rb+‐blocking reaction ranges between 1·4 and 5·4 mM, and is lower in low‐Na+, high‐K+ solutions.6. A possible characterization of the if channel which explains these results includes an inner ‘blocking’ site, to which external Cs+ ions bind, blocking the channel, and a more external ‘activatory’ site, to which K+, Cs+, Rb+ and possibly Na+ ions bind. Binding of K+ to this site induces a current increase either by modulating the channel, or actually by opening the channel itself. A similar mechanism can apply to Cs+ and to Rb+ binding.
Enhancement of calcium current during digitalis inotrophy in mammalian heart: positive feed‐back regulation by intracellular calcium?
Authors: Marban Eduardo , Tsien Richard W. 
Published: December 2014

1. Effects of digitalis compounds on slow inward Ca current Isi) and contractile force were examined in ferret ventricular muscle (single sucrose‐gap voltage clamp) and calf Purkinje fibres (two micro‐electrode voltage clamp).2. In ventricular muscle, ouabain increased Isi and inward current tails associated with Isi conductance. The enhancement of Isi followed a time course similar to the development of the positive inotropic effect, and it could be observed in the absence of aftercontractions or other signs of toxicit.3. The response of myocardial Isi and twitch force to ouabain depended strongly on a previous history of driven action potentials.4. Veratridine, a toxin that promotes Na entry through tetrodotoxin‐sensitive channels, also increased Isi and twitch force in driven ventricular muscle preparations.5. The effects of ouabain, action potential stimulation and veratridine are consistent with reported effects of K‐poor solutions in indicating that elevation of intracellular Na can lead to enhancement of Isi. Additional experiments suggest that the link between Nai and Isi involves intracellular Ca.6. When Cs‐loaded Purkinje fibres were bathed in solutions containing Sr instead of Ca, enhancement of Isi by strophanthidin was abolished even though a positive inotropic response persisted.7. After intracellular injection of Purkinje fibres with EGTA, Isi no longer increased with strophanthidin, although it remained responsive to adrenaline.8. Clear‐cut increases in Isi were seen in Cs‐loaded Purkinje fibres even at very low concentrations of strophanthidin (20‐50 nM), where the occurence of Na pump inhibition has been questioned.9. Positive regulation of Ca entry by intracellular Ca may act as a facilitory mechanism that amplifies myocardial responsiveness to digitalis and other inotropic interventions. Through changes in Isi, small rises in diastolic free Ca might lead to large increases in the activator Ca transient during contraction.
The effects of changes in osmolality and sodium concentration on angiotensin‐induced drinking and excretion in the pigeon
Authors: Fitzsimons J. T. , Massi M. , Thornton S. N. 
Published: December 2014

1. The pigeon drank copiously after a short latency in response to intracerebro‐ventricular (I.C.V.) infusion of angiotensin II dissolved in isotonic NaCl. There were small, insignificant increases in urinary excertion so that the increased water intake caused the pigeon to go into positive fluid balance. Water was chosen in preference to 0·3 M‐NaCl, which was also available to drink in these experiments.2. I.C.V. infusion of angiotensin dissolved in water, or in isotonic or hypertonic solutions of non‐eletrolytes, or in KCl or CaCl2 resulted in about half the water intake produced by angiotensin dissolved in isotonic NaCl.3. I.C.V. infusion of hypertonic NaCl alone caused drinking. I.C.V. infusion of angiotensin dissolved in hypertonic NaCl caused an amount of water to be drunk that was a simple addition of the amounts drunk in response to angiotensin dissolved in isotonic NaCl and to the extra amount of NaCl.4. Drinking in response to I.C.V. infusion of two other dipsogenic peptides, eledoisin and physalaemin, was similarly affected by the composition of the solutions in which they were dissolved.5. The pigeon also drank in response to intravenous (I.V.) infusion of angiotensin II dissolved in isotonic NaCl. Urine flow and sodium excretion increased markedly so that the pigeons just maintained fluid balance.6. In contrast to the reduction in intake when angiotensin was infused I.C.V. dissolved in hypertonic non‐electrolytes, I.V. infusions of angiotensin dissolved in hypertonic non‐electrolytes caused enhanced drinking, compared with the corresponding infusions of angiotensin dissolved in isotonic NaCl.7. Drinking induced by I.V. infusion of angiotensin was little affected by simultaneous I.C.V. infusion of isotonic or hypertonic sucrose, or water, but it was increased by simultaneous I.C.V. infusion of hypertonic NaCl.8. Drinking responses were partly additive when angiotensin was given by simultaneous I.C.V. and I.V. infusion.9. The increased urine flow and electrolyte excretion in response to I.V. infusion of angiotensin were little affected by simultaneous I.C.V. infusion of angiotensin.10. These experiments suggest that in the pigeon there may be separate sets of receptors in the cerebral ventricles for initiating drinking, one set responding to angiotensin, another to hypertonic NaCl. Outside the blood—brain barrier, and accessible to blood‐borne substances, there may also be separate sets of receptors, one set responding to angiotensin, another to increases in effective osmolality of the blood.
Occlusion of rubidium ions by the sodium‐potassium pump: its implications for the mechanism of potassium transport
Authors: Glynn I. M. , Richards D. E. 
Published: December 2014

1. The occlusion of rubidium ions by Na, K‐ATPase has been investigated by suspending enzyme prepared from pig kidney outer medulla in media containing low concentrations of 86Rb, forcing the suspensions rapidly through small columns of cation‐exchange resin, and measuring the amounts of radioactivity emerging from the columns.2. When the suspension media contained 2 mM‐ATP or ADP, or 15 mM‐NaCl, the amounts of radioactivity emerging from the columns were greatly (and similarly) reduced, presumably because both nucleotides and sodium ions stabilized the enzyme in the E1 form. (See p. 19 for definition of E1 and E2). The extra radioactivity carried through the columns when nucleotides and sodium were absent was taken as a measure of the amount of rubidium occluded within the enzyme (in the E2 form) when it emerged from the resin.3. By varying the flow rate, and therefore the time spent by the enzyme on the resin, and relating this to the amount of radioactivity emerging from the columns, we have been able to estimate the rate constant for the conformational change (E2 → E1) that allows the occluded rubidium ions to escape. At 20 °C, and in the absence of nucleotides, it is about 0·1 S−1.4. The rate constant for rubidium release was the same in a sodium‐containing as in a potassium‐containing medium. The opposite effects of sodium and potassium ions on the poise of the equilibrium between the E1 and the E2 forms of the enzyme must, therefore, be due solely to opposite effects of these ions on the rate of conversion of E1 to E2.5. The rate constant for rubidium release was greatly increased by ATP and by ADP. Both nucleotides appeared to act at low‐affinity sites and without phosphorylating the enzyme.6. Orthovanadate, in the presence of magnesium ions, stabilized the enzyme in the occluded‐rubidium (E2Rb) form.7. Ouabain, in the presence of magnesium ions, prevented the occlusion of rubidium ions.8. We have measured the amount of rubidium occluded by the enzyme as a function of rubidium concentration, and estimate that at saturating rubidium concentrations about three rubidium ions can be occluded per phosphorylation site (or per ouabain‐binding site).9. We have found that the occluded‐rubidium form of the enzyme can also be formed by allowing rubidium ions to catalyse the hydrolysis of phosphoenzyme generated by the addition of ATP to enzyme suspended in a high‐sodium medium.10. The properties of the occluded‐rubidium form of the enzyme, and of the two routes that can lead to its formation, suggest that an analagous occluded‐potassium form plays a central role in the transport of potassium ions through the sodium—potassium pump. This hypothesis is supported by a detailed consideration of the probable magnitudes of the rate constants of the individual reactions making up the two routes.
Parotid responses to stimulation of the parasympathetic innervation in bursts in weaned lambs
Authors: Andersson P.‐O. , Bloom S. R. , Edwards A. V. 
Published: December 2014

1. The effects of stimulation of the peripheral end of the parotid nerve in 1 sec bursts at 10 sec intervals has been investigated in weaned Suffolk lambs 3‐4 months after birth.2. Stimulation in bursts at either 10 or 20 Hz for 10 min produced a significantly greater flow of parotid saliva, output of Na+ and K+ and fall in parotid vascular resistance (p.v.r) than continuous stimulation at the corresponding constant frequency (1 or 2 Hz) for the same period.3. Stimulation at 40 Hz in bursts for the same period produced a significantly greater output of K+ and fall in p.v.r. than continuous stimulation at 4 Hz, whereas the salivary flow rates and Na+ outputs were closely similar.4. Comparison of the effects of stimulation of the parotid nerve in bursts over a wide range of frequencies showed that each of these parotid responses was maximal at about 80 Hz.5. Parotid salivary responses to continuous stimulation of the parotid nerve at 20 Hz for 10 min were effectively abolished by prior administration of atropine (> 1·0 mg/kg), whereas the percentage fall in p.v.r. was merely reduced from 80·2±3·6 to 33·1±8·3% under the same conditions. There was no significant change in the mean arterior‐venous difference in the plasma concentration of vasoactive intestinal peptide, substance P or somatostatin, in either the presence or absence of atropine in these experiments.6. The results are discussed in relation to the proposition that the enhancement of parotid responses which is observed during intermittent stimulation of the parasympathetic innervation at relatively high frequencies under experimental conditions also occurs normally in conscious sheep.
Non‐adrenergic inhibitory nerves and putative transmitters in the smooth muscle of cat trachea
Authors: Ito Yushi , Takeda Kazuo 
Published: December 2014

1. Effects of non‐adrenergic non‐cholinergic inhibitory nerve stimulation on the smooth muscle of the cat trachea were studied in vitro using micro‐electrode, double sucrose‐gap and tension recording methods.2. Electrical field stimulation with a short pulse (50 μs) evoked an excitatory junction potential (e.j.p.) followed by a twitch, with or without a subsequent small, long‐lasting relaxation. This response was abolished by tetrodotoxin (5 × 10−7 M).3. After pre‐treatment with atropine (10−7 to 5 × 10−6 M) both e.j.p. and twitch tension were selectively blocked and repetitive stimuli at 20 Hz evoked in some preparations slow membrane hyperpolarization followed by long‐lasting relaxation. These effects were abolished by propranolol (2 × 10−6 M). In the presence of atropine (10−6 M) and propranolol (2 × 10−6 M) field stimulation caused no detectable change in tension, membrane potential or membrane resistance.4. 5‐Hydroxytryptamine (5‐HT) (10−6 to 5 × 10−6 M) produced a tonic contracture of the cat trachea. In the presence of atropine, field stimulation induced a marked reduction in the amplitude of the contracture which was only partly suppressed by propranolol (5 × 10−6 M). During this muscle relaxation, produced by field stimulation in the presence of 5‐HT, atropine and propranolol, there was no apparent change in the membrane potential or in membrane resistance. The magnitude of the relaxation was proportional to the number of stimuli applied.5. ATP (< 10−3 M) and VIP (< 10−9 M) had no effect on the membrane potential or resistance of the smooth muscle cells of the cat trachea, although higher concentrations of VIP (> 10−8 M) hyperpolarized the membrane and reduced the membrane resistance. Low concentrations, i.e. ATP 5 × 10−6 M or VIP 10−12 M, which had no effects in the electrical membrane properties, caused relaxation of the muscle contracture evoked by 5‐HT.6. After desensitization to exogenous ATP or adenosine, in the presence or absence of dipyridamole (2 × 10−7 M), the amplitude of the muscle relaxation evoked by the activation of non‐adrenergic inhibitory nerves was not affected. It was, however, much smaller during partial desensitization to VIP.7. These results indicate that cat tracheal smooth muscles are innervated by non‐adrenergic, non‐cholinergic inhibitory nerves, which cause muscle relaxation without affecting the electrical membrane properties. The possible involvements of ATP or VIP in the inhibitory nervous transmission is discussed.
M‐currents and other potassium currents in bullfrog sympathetic neurones
Authors: Adams P. R. , Brown D. A. , Constanti A. 
Published: December 2014

1. Bullfrog lumbar sympathetic neurones were voltage‐clamped in vitro through twin micro‐electrodes. Four different outward (K+) currents could be identified: (i) a large sustained voltage‐sensitive delayed rectifier current (IK) activated at membrane potentials more positive than ‐25 mV; (ii) a calcium‐dependent sustained outward current (IC) activated at similar positive potentials and peaking at +20 to +60 mV; (iii) a transient current (IA) activated at membrane potentials more positive than ‐60 mV after a hyperpolarizing pre‐pulse, but which was rapidly and totally inactivated at all potentials within its activation range; and (iv) a new K+ current, the M‐current (IM).2. IM was detected as a non‐inactivating current with a threshold at ‐60 mV. The underlying conductance GM showed a sigmoidal activation curve between ‐60 and ‐10 mV, with half‐activation at ‐35 mV and a maximal value (ḠM) of 84±14 (S.E.M.) nS per neurone. The voltage sensitivity of GM could be expressed in terms of a simple Boltzmann distribution for a single multivalent gating particle.3. IM activated and de‐activated along an exponential time course with a time constant uniquely dependent upon voltage, maximizing at ≃ 150 ms at ‐35 mV at 22 °C.4. Instantaneous current—voltage (I/V) curves were approximately linear in the presence of IM, suggesting that the M‐channels do not show appreciable rectification. However, the time‐ and voltage‐dependent opening of the M‐channels induced considerable rectification in the steady‐state I/V curves recorded under both voltage‐clamp and current‐clamp modes between ‐60 and ‐25 mV. Both time‐ and voltage‐dependent rectification in the voltage responses to current injection over this range could be predicted from the kinetic properties of IM.5. It is suggested that IM exerts a strong potential‐clamping effect on the behaviour of these neurones at membrane potentials subthreshold to excitation.