bluuebunny/crossref_metadata_2025 huggingface dataset:
Inositol 1,4,5‐trisphosphate activates pharmacomechanical coupling in smooth muscle of the rabbit mesenteric artery.
Authors: Hashimoto T , Hirata M , Itoh T , Kanmura Y , Kuriyama H
Published: December 2014

To clarify the nature of the noradrenaline (NA)‐induced contraction, the effects of NA on inositol phospholipid metabolism and the actions of inositol 1,4,5‐trisphosphate (InsP3) on skinned muscle of the rabbit mesenteric artery were investigated. NA, in concentrations over 1 nM, reduced the amount of phosphatidylinositol 4,5‐bisphosphate (PI‐P2) and increased the amount of phosphatidic acid (PA). The maximum reduction in the amount of PI‐P2 and the maximum increase in the amount of PA were observed in the presence of 1 microM‐NA. With prolonged application of NA, the PI‐P2 was gradually restored to near the control level, but with repeated applications of NA separated by rinses with Krebs solution, there was a consistent reduction of PI‐P2. The NA‐induced PI‐P2 breakdown was inhibited by the alpha 1‐adrenoceptor blocking agent, prazosin. After incubation of the tissue with radioactive inositol‐containing solution, NA transiently increased the amount of radioactive InsP3 which was followed by increases in the amount of inositol 1,4‐bisphosphate (InsP2) and inositol monophosphate (InsP). After accumulation of Ca by saponin‐treated muscle cells of the dog mesenteric artery dispersed by collagenase, InsP3 released Ca stored in cells but InsP2 did not. A23187 (5 microM) but not InsP3 (up to 10 microM), depleted Ca accumulated in the presence of ATP. In saponin‐treated skinned muscle tissues, InsP3 in concentrations over 0.3 microM, produced contraction following accumulation of Ca into the store site. InsP3 released Ca from the same source as caffeine. The release of Ca by InsP3 appeared in a concentration‐dependent manner and this release also depended on the amount of Ca stored in cells (the median effective dose (ED50) was 3.0 microM in 0.1 microM‐Ca and 1.0 microM in 0.3 microM‐Ca). We concluded that NA activates alpha 1‐adrenoceptors, thus hydrolysing PI‐P2 and synthesizing InsP3. This product can release Ca stored in cells as estimated from the contraction in skinned muscle tissues, and also reduces the residual amount of Ca stored in skinned dispersed muscle cells. Contraction evoked by NA through pharmacomechanical coupling can be explained as a function of InsP3.
Enzyme activities in single electrophysiologically identified crab muscle fibres.
Authors: Maier L , Pette D , Rathmayer W
Published: December 2014

The superficial muscle fibres in the proximal part of the closer muscle in the crab Eriphia can be separated into four fibre groups (I‐IV) on the basis of electrophysiological and histochemical characteristics. The activity levels of glyceraldehydephosphate dehydrogenase (GAPDH), lactate dehydrogenase (LDH), citrate synthase (CS), NADP‐isocitrate dehydrogenase (IDH) and 3‐hydroxyacyl‐CoA dehydrogenase (HAD), determined in single electrophysiologically identified fibres, differed significantly among the different fibre groups. In addition, fibres belonging to the same group, with similar electrophysiological characteristics, demonstrated variability with regard to metabolic enzyme activities. Nevertheless, comparison of absolute enzyme activities and enzyme activity ratios permitted the discrimination of at least three groups. These groups corresponded with those defined according to electrophysiological and histochemical characteristics. The group I fibres (tonic fibres) are intermediate in oxidative potential and show the lowest values of glycolytic enzymes. The group II and group III fibres can be regarded as fast oxidative fibres. The high ratio between activity levels of enzymes for glycolytic and oxidative metabolism found for group IV fibres (fast fibres) demonstrated that this group depends strongly on anaerobic metabolism.
Spatial and temporal limits of vision in the achromat.
Authors: Hess R F , Nordby K
Published: December 2014

Threshold detection for sine‐wave grating stimuli of varying spatial and temporal frequency was used to investigate the nature of spatial and temporal post‐receptoral sensitivity in the typical, complete achromat. Threshold spatial and temporal sensitivities under low photopic conditions show no evidence of cone function. The abrupt fall‐off in sensitivity is consistent with known psychophysical and electrophysiological measures of rod saturation. Threshold spatial and temporal sensitivities under scotopic conditions are identical in form and absolute sensitivity to that of the normal scotopic system. Spatial and temporal acuity measurements substantiate the above conclusions based on contrast sensitivity. We conclude that the typical and complete achromat possesses only a normal functioning rod post‐receptoral mechanism.
Effect of trifluoperazine on rabbit cortical collecting tubular response to vasopressin.
Authors: Dillingham M A , Dixon B S , Kim J K , Wilson P D
Published: December 2014

Anuran membrane studies suggest that the calcium‐binding protein calmodulin is necessary for arginine vasopressin (AVP) to exert a hydro‐osmotic effect. We therefore examined the effect of trifluoperazine and N‐(6‐aminohexyl)‐5‐chloro‐1‐naphtholene sulphonamide (W‐7), chemically dissimilar calmodulin inhibitors, on hydraulic conductivity (Lp) response to AVP in rabbit cortical collecting tubules perfused in vitro. Trifluoperazine but not W‐7 increased basal Lp in rabbit cortical collecting tubules. When cortical collecting tubules were pre‐treated with either trifluoperazine or W‐7, the effect of AVP to increase Lp was significantly inhibited. To determine the site of this inhibition, Lp responses to exogenous cyclic adenosine 3',5'‐phosphate (AMP) were studied. Both trifluoperazine and W‐7 pretreatment significantly inhibited the effect of a cyclic AMP analogue to increase rabbit cortical collecting tubule Lp. These results suggest that calmodulin may be an important mediator of the hydro‐osmotic response to AVP in the mammalian cortical collecting tube by acting at a site or sites distal to cyclic AMP formation.
Oxygen consumption and active sodium and chloride transport in bovine tracheal epithelium.
Authors: Durand J , Durand-Arczynska W , Schoenenweid F
Published: December 2014

The O2 consumption (Jr) and the short‐circuit current (Ji) were measured simultaneously in bovine tracheal epithelium in vitro. In this tissue, Ji is the sum of two active transport processes, Cl‐ secretion and Na+ absorption. Jr was determined from the decrease of PO2 in the incubation solution, at 37 +/‐ 0.05 degrees C and at a PO2 around 600 torr. Microbial contamination and leaks of dissolved O2 from the solution never exceeded 4% of the rate of PO2 decrease due to the O2 consumption of the tissue. Ji and Jr were stable over 5 h of incubation under standard conditions. Ji was 106 +/‐ 4 nequiv min‐1 cm‐2 and Jr was 39.8 +/‐ 1.1 nmol O2 min‐1 cm‐2 (mean +/‐ S.E., n = 46). Ji was varied with several agents known to affect ion transport across the tracheal epithelium. Na+ absorption was inhibited partly with amiloride or completely following Na+ substitution with choline. Cl‐ secretion was selectively suppressed by furosemide. Ji was also reduced to a very low level, using ouabain or K+ suppression to inhibit the Na+‐K+‐ATPase. All these manoeuvres resulted in significant reductions of both Ji and Jr. Basal Jr was not affected when Ji was modified. A plot of the relative change in suprabasal Jr versus the relative change of Ji gave a straight line (r = 0.98, n = 60). A plot using absolute values yielded a stoichiometric ratio of 13.9 ions per O2 molecule, for Na+ as well as for Cl‐. The stoichiometric ratio was also calculated for each experiment. Its mean value was 14.9 ions per O2 molecule. The population of the ratios was widely dispersed, but this was explained as a predictable statistical phenomenon.
The removal of myoplasmic free calcium following calcium release in frog skeletal muscle.
Authors: Melzer W , Ríos E , Schneider M F
Published: December 2014

Transient changes in intracellular free calcium concentration (delta [Ca2+]) in response to pulse depolarizations were monitored in isolated segments of single frog skeletal muscle fibres cut at both ends and voltage clamped at a holding potential of ‐90 mV in a double‐Vaseline‐gap chamber. Calcium transients were monitored optically using the metallochromic indicator dye Antipyrylazo III (APIII), which entered the fibre by diffusion from the solution applied to the cut ends. Optical artifacts due to fibre movement were minimized or eliminated by stretching the fibres to sarcomere lengths at which there was little or no overlap of thick and thin contractile filaments. Remaining movement‐independent optical changes intrinsic to the fibre and unrelated to the dye were monitored at 850 nm, where free and dye‐bound APIII have no absorbance. These 850 nm signals scaled by lambda ‐1.2 were used to remove intrinsic components from the signals at 700 or 720 nm, wave‐lengths at which the APIII absorbance increases when calcium is bound. The corrected 700 or 720 nm signals were used to calculate delta [Ca2+]. The decay of delta [Ca2+] following fibre repolarization at the termination of a depolarizing pulse was well described by a single exponential plus a constant. The exponential rate constant for the decay of delta [Ca2+] decreased and the final 'steady' level that delta [Ca2+] appeared to be approaching increased with increasing amplitude and/or duration of the depolarizing pulse. Both the decreasing decay rate and the build up of the 'steady' level can be accounted for using a two‐component model for the removal of free calcium from the myoplasm. One component consists of a set number of a single type of saturable calcium binding site in the myoplasm. The second component is a non‐saturable, first‐order uptake mechanism operating in parallel with the saturable binding sites. The removal model parameter values were adjusted to fit simultaneously the decay of delta [Ca2+] after pulses of various amplitudes and durations in a given fibre. The basic procedure was to track delta [Ca2+] during each pulse when an undetermined calcium release was occurring, but to calculate the decay of delta [Ca2+] starting 14 ms after repolarization when release was assumed to be negligible. After appropriate selection of parameter values, the model reproduced most aspects of the decay of delta [Ca2+].(ABSTRACT TRUNCATED AT 400 WORDS)
Calcium action potentials and calcium currents in tonic muscle fibres of the frog (Rana pipiens).
Authors: Huerta M , Stefani E
Published: December 2014

Slow action potentials were evoked in cruralis tonic and twitch fibres of the frog after drastically reducing the Cl‐ and K+ conductances. Tonic fibres were identified by their electrical characteristics. They had an effective resistance (Reff) of 50 +/‐ 6 M omega (n = 27) and a membrane time constant (tau m) of 440 +/‐ 70 ms (n = 8). In twitch fibres Reff = 2.9 +/‐ 0.3 M omega (n = 16) and tau m = 50 +/‐ 4 ms (n = 6). In tonic fibres the slow action potential had a threshold of ‐50 to ‐60 mV and a peak amplitude of ‐10 mV. In twitch fibres the slow action potential had a threshold of ‐40 mV and reached a peak amplitude of +40 mV. The responses were blocked by the addition of Cd2+ (2 mM) or Co2+ (5 mM). These results strongly suggest that Ca2+ is the main carrier of current during the response. Using the three‐micro‐electrode voltage‐clamp technique a slow inward membrane current underlying the Ca2+ potential could be described in tonic muscle fibres. The slow inward current was mainly carried by Ca2+, since it was reduced when external Ca2+ concentration was lowered or when Cd2+ (2 mM) was added. Moreover, Ca2+ was the only cation in the solution that could carry inward current. It had a mean threshold of ‐60 mV, reached a maximum value at ca. 0 mV, ranged from 24 to 28 microA/cm2 and had a mean reversal potential of +35 mV. In about half of the examined tonic fibres inward current declined with time, only slowly. This can either be explained by there being less contamination by K+ outward current, or by the presence of two types of Ca2+ channels in the tonic fibre membrane.
Calcium uptake of rat brain synaptosomes as a function of membrane potential under different depolarizing conditions.
Authors: Adam-Vizi V , Ligeti E
Published: December 2014

The uptake of 45Ca2+ was measured in brain synaptosomes under conditions designed to depolarize the membranes. Membrane potential was estimated from the distribution of 86Rb+ between the intra‐ and extracellular compartments. K+ depolarization (8‐60 mM) only increased "a2+ uptake beyond a threshold depolarization of about 10 mV, whereas veratridine (5‐40 microM) induced an increased Ca2+ uptake at a concentration which depolarized the membrane less than this threshold. Ouabain did not enhance Ca2+ uptake, but the depolarization it produced did not reach threshold. Ca2+ influx already stimulated by K+ depolarization can be further enhanced by veratridine without any parallel change in membrane potential. Only the pathway mediating Ca2+ uptake during K+ depolarization can be inactivated: Ca2+ uptake evoked by K+ depolarization is decreased in synaptosomes pre‐depolarized in the presence of a high concentration of K+. In contrast, pre‐depolarization does not change Ca2+ uptake evoked by veratridine. Ca2+ channel blockers, such as verapamil and diltiazem but not nifedipine, in concentrations of 10‐100 microM, decrease the stimulation of Ca2+ uptake by high K+ concentration without influencing depolarization, whereas the effect of veratridine on Ca2+ uptake is only inhibited when its effect on Na+ channels is also prevented. It is concluded that Ca2+ uptake during K+ depolarization proceeds through voltage‐dependent Ca2+ channels similar to those of squid axon, whereas veratridine activates an additional Ca2+ entry, possibly via influx through open Na+ channels. Different quantitative relationships are found between acetylcholine release of synaptosomes and the amount of Ca2+ taken up by different mechanisms: the same amount of Ca2+ uptake is accompanied by a greater increase of acetylcholine release if the uptake is induced by K+ depolarization rather than veratridine.
The effects of arterial blood gas tensions on pressor responses to angiotensin II in the pithed rat.
Authors: Grant T L , McGrath J C
Published: December 2014

The influence of arterial blood gas tensions on angiotensin II‐mediated pressor responses in the pithed rat was studied by altering the inspired gas mixture at a fixed tidal volume. When rats were ventilated to produce physiological Pa, CO2 levels (35‐40 mmHg) responses to boluses of angiotensin II were greater with increasing Pa, O2 over the Pa, O2 range of 65‐460 mmHg. There was no difference in response to angiotensin II over the Pa, CO2 range studied (18‐50 mmHg). All variations in response to angiotensin II were attributable to changes in Pa, O2. Since arterial blood gas tensions, especially the Pa, O2, modulate pressor responses to boluses of angiotensin II, the physiological effects of this hormone may be most fruitfully explored in rats ventilated to produce normal arterial blood gas tensions.
Characteristics of phasic and tonic sympathetic ganglion cells of the guinea‐pig.
Authors: Cassell J F , Clark A L , McLachlan E M
Published: December 2014

Intracellular recording techniques have been used to determine the electrophysiological properties of sympathetic neurones in ganglia of the caudal lumbar sympathetic chain (l.s.c.) and in the distal lobes of inferior mesenteric ganglia (i.m.g.) isolated from guinea‐pigs. Passage of suprathreshold depolarizing current initiated transient bursts of action potentials in 97% of l.s.c. neurones, but only 13% of i.m.g. cells ('phasic' neurones). Most i.m.g. neurones fired continuously during prolonged depolarizing pulses ('tonic' neurones). Passive membrane properties varied; mean cell input resistance was similar between groups, but phasic neurones had smaller major input time constants on average than had tonic cells. Current‐voltage relations determined under both current clamp and voltage clamp were linear around resting membrane potential (approximately 60 mV), where membrane conductance was lowest. Instantaneous and time‐dependent rectification varied in the different neurone types. The current underlying the after‐hyperpolarization following the action potential was significantly larger on average in tonic i.m.g. cells than in phasic neurones, although its time course (tau = 100 ms) was similar. Phasic neurones fired tonically when depolarized after adding the muscarinic agonist, bethanechol (10(‐5) M to 10(‐4) M), to the bathing solution. Bethanechol blocked a proportion of the maintained outward current (presumably the M‐current, IM, Adams, Brown & Constanti, 1982) in phasic neurones; this current was small or absent in tonic neurones. Transient outward currents resembling the A‐current (IA, Connor & Stevens, 1971 a) were evoked in tonic but not in phasic neurones by depolarization from resting membrane potential. IA could only be demonstrated in phasic neurones after a period of conditioning hyperpolarization. After a step depolarization to approximately ‐‐50 mV, IA reached peak amplitude at about 7 ms and then decayed with a time constant of about 25 ms in both neurone types. Activation characteristics of IA were similar for phasic and tonic neurones, but inactivation curves, although having the same shape, were shifted to more depolarized voltages in tonic neurones. That is, IA was largely inactivated at resting membrane potential in phasic, but not tonic neurones. It is concluded that the discharge patterns of the two populations of sympathetic neurones result from differences in the voltage‐dependent potassium channels present in their membranes. The anatomical occurrence of the different cell types suggests that phasic neurones are vasoconstrictor and tonic neurones are involved with visceral motility.
Responses of spinal cord neurones to stimulation of articular afferent fibres in the cat.
Authors: Schaible H G , Schmidt R F , Willis W D
Published: December 2014

Responses of spinal cord neurones to excitatory input from myelinated and non‐myelinated afferent fibres of the knee joint were investigated in spinalized cats that were anaesthetized with alpha‐chloralose. The hind limb was largely denervated except for the knee joint. The action of joint afferent volleys on populations of spinal cord neurones was assessed by recordings of cord dorsum potentials and of field potentials within the substance of the spinal cord. Three different negative cord dorsum potentials (NI, NII and NIII waves) were produced by volleys in progressively smaller sized myelinated afferent fibres of the posterior articular nerve of the knee. Volleys in non‐myelinated joint afferent fibres did not evoke a detectable cord dorsum potential. The NII and NIII waves could be recorded at segmental levels L4‐S2. Field potentials corresponding to the cord dorsum negative waves were recorded with a tungsten micro‐electrode inserted into the substance of the cord. The potentials were negative when the recording electrode was in the dorsal horn, but reversed to become positive in the ventral horn. There were differences in the depths at which the different components of the field potential sequence reversed in sign. Single unit recordings revealed that afferent volleys in the posterior articular nerve could excite neurones in segments L5‐S1 and at depths from less than 1 to 4 mm below the dorsal surface of the cord. Most marked recording sites were in laminae I, IV‐VI or VIII. Many units were activated just by the A fibre component of the joint afferent volley, but others could also be excited by the C fibre component. None were excited just by C fibres. All units tested had a convergent excitatory input from fibres belonging to cutaneous, muscle and mixed nerves. Neurones excited by joint afferent volleys were tested for a receptive field using several forms of local mechanical stimulation of the knee joint and joint movements. Most cells could be activated by one or more of these stimuli. Although many of the effective mechanical stimuli were innocuous, noxious stimuli could often excite the cells more effectively, and some neurones were only activated by noxious stimuli. A few cells with receptive fields in the knee joint did not respond to joint movements.
Tension transients during the rise of tetanic tension in frog muscle fibres.
Authors: Ford L E , Huxley A F , Simmons R M
Published: December 2014

Tension transients were recorded from fibres isolated from the tibialis anterior muscle of the frog during the rise of tetanic tension at 0.8‐2.5 degrees C. The length of a central segment of the fibre was controlled by feed‐back from a spot‐follower device. Length steps complete within 0.2 ms were applied at one end of the fibre, and tension changes were recorded at the other end with a transducer having a natural frequency of 10.8 kHz. The tension transients measured during the rise of force showed the four phases characteristic of transients recorded during the plateau of a tetanus and during shortening. The extreme tension change reached during a length change was smaller for a given size of step during the rise of tension than at the plateau, but by less than in proportion to the developed force, suggesting that stiffness increases earlier than tension. Stiffness changes were further assessed by matching the tension records from one fibre with the responses of an analogue circuit (delay line) representing the mechanical properties of the fibre and force transducer. Stiffness derived from these comparisons varied in approximately the same proportion as stiffness assessed from the extreme tension change. During the rise of tension, there was a roughly constant lag of tension behind stiffness, ranging from 11 to 16 ms in different fibres. Steps applied during the latent period showed a lag of about 10 ms from the first increase of stiffness to the first appearance of tension. The partial recovery of tension immediately following the step, phase 2, was faster at the low tension levels early in the tetanus. The intermediate level, T2, to which tension recovers during phase 2 scaled in approximate proportion to the tension level immediately preceding the step. This result is unlike the relative decrease in T2 levels we have recently described for steps applied during steady shortening, and suggests that the increased stiffness‐tension ratio seen during the rise of tetanic force is not due to shortening within the sarcomeres. The results can be explained if the attachment of cross‐bridges in the rising phase takes place in two steps, the initial state of attachment resulting in the production of little or no tension. Several such schemes are considered.
Autonomic mechanisms underlying capsaicin induced oral sensations and salivation in man.
Authors: Dunér-Engström M , Fredholm B B , Larsson O , Lundberg J M , Saria A
Published: December 2014

The effects of capsaicin, citric acid and nicotine applied to the apex or radix of the tongue on taste sensations and salivation were studied in relation to the presence of substance P immunoreactive neurones in man. Application of capsaicin (30 micron) to the apex of the tongue or to the palatinal mucosa, but not to the radix of the tongue, caused a reproducible burning sensation and salivation from the submandibular‐sublingual and parotid glands. The salivation response to capsaicin was reduced by methylscopolamine pretreatment. Similar levels of substance P immunoreactivity were present in the lingual apex and radix area (including vallate papillae) of man, while in the cat about 4 times higher levels of substance P immunoreactivity were present in the vallate papillae than in the lingual apex. Immunohistochemistry showed that in the cat many substance P immunoreactive nerves were associated with the taste buds of the vallate papillae, while in man substance P immunoreactive fibres were only seen penetrating into the epithelium of the lingual apex. In addition some subepithelial blood vessels in all regions were surrounded by substance P immunoreactive nerves in both cat and man. Citric acid application to the tongue apex caused both submandibular‐sublingual and parotid salivary secretion concomitant with a burning sensation. Salivary secretion was also seen after citric acid application to the radix of the tongue. This response was associated with a sour taste. The salivation response to citric acid was not significantly reduced by methylscopolamine pretreatment. Lingual apex application of nicotine was associated with a sweet taste and a small rise in salivary secretion rate. This response was not significantly reduced by methylscopolamine. In conclusion, the sensitivity to capsaicin of the human tongue is restricted to the apex portion. This is in parallel with the occurrence of intraepithelial substance P immunoreactive nerve fibres. Capsaicin induced salivary secretion seems mainly to be mediated via parasympathetic, cholinergic reflex mechanisms. Citric acid and nicotine induced salivation responses are comparatively more resistant to methylscopolamine pretreatment.
Activation of acetylcholine receptors on clonal mammalian BC3H‐1 cells by low concentrations of agonist.
Authors: Sine S M , Steinbach J H
Published: December 2014

The patch‐clamp technique was used to examine the activation of single acetylcholine receptor channels of clonal BC3H‐1 mouse muscle cells. Single‐channel currents were activated by low concentrations of the strong agonists acetylcholine (ACh, 50‐100 nM), carbamylcholine (1‐2 microM), and suberyldicholine (30‐50 nM). At low agonist concentrations channel openings occur as isolated short‐duration openings and as bursts of longer duration openings separated by brief closed periods. Two distinct types of brief closed periods separate long duration openings: brief closures (mean duration, 50 microseconds) and intermediate closures (mean duration, 0.5‐1.0 ms). The kinetic properties of intermediate closures depend on the agonist, suggesting that they reflect receptor reopening from the closed state leading to the open state. Properties of brief closures, in contrast, are independent of the agonist, indicating that they result from an additional closed state leading away from the pathway producing the open state. A receptor activation scheme is proposed which accounts for the observed closed states, and transition rate estimates are presented for steps within the proposed scheme. The channel opening rate, beta, differs several‐fold for the agonists studied (200‐1400 s‐1) and is comparable to the dissociation rate, k‐2 (900 s‐1). The dissociation rate is similar for the three agonists studied. The channel closing rate, alpha, is much slower than the opening rate (20‐60 s‐1). The probability is high that a doubly liganded channel is in the open state and depends on the agonist (0.75‐0.97). Beta increases and alpha decreases at more negative membrane potentials, whereas k‐2 shows little potential dependence.
Sodium/calcium exchange and intracellular calcium buffering in ferret myocardium: an ion‐sensitive micro‐electrode study.
Authors: Chapman R A
Published: December 2014

Measurements of the intracellular activity of Ca (aiCa), Na (aiNa) and H (pHi) ions have been made with resin‐filled ion‐sensitive micro‐electrodes in ferret ventricular trabeculae. The mean values in quiescent muscle at 30 degrees C were: aiNa, 11.1 +/‐ 1.0 mM; aiCa, 58.4 +/‐ 6.4 nM, and pHi, 7.20 +/‐ 0.11. The relation between aiNa and extracellular Na activity (aoNa) is not linear and is sensitive to temperature: the Q10 for the change in aiNa in normal Tyrode solution is 1.3 +/‐ 0.5 and rises to 3.5 +/‐ 0.5 when aoNa is reduced to 1.1 mM. The addition of CN to the bathing fluid causes little or no change in aiNa or aiCa but pHi rises to 7.38 +/‐ 0.10, yet in some preparations resting tension increases. Similar results are seen with carbonyl cyanide m‐chlorophenyl hydrazone. On lowering [Na]o, the fall in aiNa is very much greater than the rise in aiCa and the pHi is generally unchanged. When [Na]o is lowered in the presence of a respiratory inhibitor, the fall in aiNa is reduced, the rise in aiCa and the contracture tension are increased while pHi falls. The apparent coupling ratio for the Na/Ca exchange varies between 3 and 4 depending on the experimental conditions. These results suggest that an intracellular process, with a high Q10 and which depends upon respiration and aiNa, is able to remove Ca2+ from the sarcoplasm and thereby interact with the sarcolemmal Na/Ca exchange. This process could be the increase in the energy‐dependent accumulation of Ca2+ within mitochondria that will occur when the Ca efflux from these organelles is progressively inhibited as aiNa falls.
Effects of hypercapnia and hypoxia on nasal vasculature and airflow resistance in the anaesthetized dog.
Authors: Lung M A , Wang J C
Published: December 2014

The experiments were performed on anaesthetized dogs which breathed spontaneously or were artificially ventilated and paralysed. The spontaneous nasal arterial blood flow was measured on one side of the nose while nasal vascular resistance was determined on the other side simultaneously. Nasal arterial blood flow was measured by means of an electromagnetic flow sensor placed around the terminal branch of the internal maxillary artery, the main arterial supply to the nasal mucosa. Nasal vascular resistance was measured by constant‐flow perfusion of the terminal branch of the internal maxillary artery. Nasal airway resistance was assessed by monitoring the transnasal pressure at constant airflow through each side of the nose simultaneously. Hypercapnic gas challenge (8% CO2, 30% O2 in N2) to the lungs increased nasal vascular resistance and decreased nasal airway resistance. Similar gas challenge to the nose did not affect nasal vascular resistance but decreased nasal airway resistance. Hypoxic gas challenge (6% O2 in N2) to the lungs did not affect the nasal vascular resistance but decreased nasal airway resistance only when the nasal vascular bed was under controlled perfusion. Similar gas challenge to the nose did not affect either nasal vascular or airway resistance. Arterial chemoreceptor stimulation by intracarotid injection of sodium cyanide increased nasal vascular resistance and decreased nasal airway resistance. The nasal vascular response to hypercapnia and arterial chemoreceptor stimulation was reflex in nature, being abolished by nasal sympathectomy. The nasal airway response to hypercapnia, hypoxia and arterial chemoreceptor stimulation was reflex in nature, being partially or completely abolished by nasal sympathectomy. Hypercapnia probably induced a local vasodilatatory effect on the capacitance vessels whereas hypoxia had no direct action on the vasculature.
Quantitative studies of the discharge fields of single cells in cat striate cortex.
Authors: Heggelund P
Published: December 2014

The configuration and width of on‐ and off‐response zones in the discharge field of single cells in cat striate cortex was analysed by quantitative methods. The responses across on‐ and off‐zones were plotted for 321 cells with a stationary optimum oriented light slit. The cells fell into two completely distinct subgroups with respect to the degree of overlap between adjacent on‐ and off‐zones. The simple cells had a mean overlap of 16.8%, the complex cells 94.5%. For simple cells the ratio between the maximum off‐ and maximum on‐response in the discharge field was bimodal, showing that two distinct subgroups termed on‐ and off‐dominant cells could be distinguished. For the complex cells the corresponding frequency distribution was unimodal. The maximum response on the two regions adjacent to the most responsive discharge zone (the dominant zone) differed markedly for most simple cells, and only a very few cells had discharge fields approximating an ideal even symmetric field. The frequency distribution of the ratio between the maximum response in the two regions was unimodal showing that odd and even symmetric fields did not form distinct subgroups of simple cells. The number of different discharge zones in simple cells varied from one to five. The zones were arranged as alternating on‐ and off‐zones across the discharge field. The maximum response in the subzones decreased with increasing sequential distance from the dominant zone, so the response pattern across each side of the discharge field resembled a damped wave‐form pattern. All the complex cells had one on‐ and off‐zone which overlapped. The mean width of the subregions in the simple cell discharge field and the mean distance between the response maxima in the subzones increased in the same proportion with increasing eccentricity. The paracentral fields were therefore like magnified central fields. The average width of the whole discharge field was not significantly different for the simple and the complex cells at the various eccentricities.
Renal electrolyte excretion and renin release during calcium and parathormone infusions in conscious rabbits.
Authors: Peart W S , Roddis S A , Unwin R J
Published: December 2014

Following a random block experimental design in each case, three repeated measurement studies were carried out in three different groups of conscious rabbits, to investigate the renal effects of increasing doses of intravenous calcium chloride (CaCl2) and bovine parathyroid hormone (PTH). In the first study, each rabbit received either CaCl2 (0.15, 0.3, 0.5 or 1.0 mg kg‐1 min‐1) or vehicle alone (control) for 160 min. In the second study, rabbits were given either PTH (0.15 microgram kg‐1 min‐1), CaCl2 (1.0 mg kg‐1 min‐1), PTH plus CaCl2 (0.15 microgram kg‐1 min‐1 and 1.0 mg kg‐1 min‐1, respectively) or vehicle alone; PTH was infused for just over 60 min. In the third study, a much smaller dose (0.05 mg kg‐1 min‐1) of CaCl2 was infused for 100 min. CaCl2 infusion produced a striking fall in fractional excretion of sodium of at least 50% (P less than 0.01), but this was not dose related, being almost maximal at the smaller doses infused. Although this effect was evident in the absence of any changes in total plasma calcium concentration at the lower doses of CaCl2, renal calcium excretion was increased between 2‐ and 20‐fold (P less than 0.01) at all doses infused. Fractional excretion of chloride doubled at the two higher doses of CaCl2 (P less than 0.01), but potassium excretion was unchanged. There were no consistent alterations in mean arterial blood pressure, effective renal plasma flow, glomerular filtration rate or plasma renin activity (PRA); total plasma calcium concentration was consistently elevated only during infusion of the high dose by just under 1 mmol l‐1. PTH infusion had no measured effect on fractional excretion of sodium or renal calcium excretion, but doubled fractional potassium excretion (P less than 0.05). Heart rate and PRA increased (P less than 0.01 and less than 0.05, respectively), the latter by 50%, but systemic pressure and renal haemodynamics were not significantly affected. By contrast, PTH infused with CaCl2 produced a 4‐fold rise in fractional sodium excretion and although renal calcium excretion remained increased, it was reduced by ca. 80% when compared with renal calcium excretion during infusion of CaCl2 alone. Infusion of PTH alone increased PRA, but when PTH and CaCl2 were infused together, PRA did not change.(ABSTRACT TRUNCATED AT 400 WORDS)
Fusimotor reflexes in triceps surae muscle elicited by stretch of muscles in the contralateral hind limb of the cat.
Authors: Appelberg B , Johansson H , Sojka P
Published: December 2014

Experiments were performed on twenty‐one cats anaesthetized with alpha‐chloralose. The aim of this study was to investigate the reflex effects on triceps surae and plantaris fusimotor neurones elicited by tonic stretch of the contralateral posterior biceps and semitendinosus (p.b.s.t.) and the contralateral triceps surae and plantaris muscles, to compare these effects with the effects evoked by flexion or extension of the intact contralateral hind limb (Appelberg, Hulliger, Johansson & Sojka, 1984) and to clarify the interactions between the reflexes from contralateral and ipsilateral muscles. Activity in fusimotor neurones was studied indirectly by recording from primary muscle spindle afferents of the triceps surae and plantaris muscle. The mean rate of firing and the modulation of the afferent response to sinusoidal extension of the triceps surae and plantaris muscles was determined. Control measurements were made with the ipsilateral p.b.s.t., the contralateral p.b.s.t. and the contralateral triceps and plantaris muscles relaxed. Tests were made with tonic stretch of one of these muscles alone or with two of them simultaneously. With stretch of the contralateral p.b.s.t. ten out of eighty‐four primary afferents (11.9%) showed predominantly dynamic reflexes (six out of forty‐one in spinalized preparations: 14.6%), twenty‐two (26.2%) showed mixed or predominantly static effects (one spinalized: 2.4%) and fifty‐two units (61.9%) showed no effect (thirty‐four spinalized: 83.0%). The reflex effects could be reproduced by electrical stimulation of the cut contralateral p.b.s.t. nerve either at group II or at group III strength. With stretch of the contralateral triceps and plantaris muscles seventy out of seventy‐six (92.1%) primary muscle spindle afferents showed no effect and six (7.9%) mixed or predominantly static reflex effects. In general, the reflex effects were not accompanied by detectable electromyographic (e.m.g.) activity in the ipsilateral triceps and plantaris (recorded with surface or needle electrodes), indicating that the reflexes mainly involved gamma‐motoneurones. The difference in efficacy between contralateral flexor (p.b.s.t.) and extensor (triceps and plantaris) muscles seems to be in accordance with the response pattern found with extension or flexion of the intact contralateral hind limb (Appelberg et al. 1984).(ABSTRACT TRUNCATED AT 400 WORDS)
Intramembrane charge movement and calcium release in frog skeletal muscle.
Authors: Melzer W , Schneider M F , Simon B J , Szucs G
Published: December 2014

Intramembrane charge movement and myoplasmic free calcium transients (delta[Ca2+]) were monitored in voltage‐clamped segments of isolated frog muscle fibres cut at both ends and mounted in a double Vaseline‐gap chamber. The fibres were stretched to sarcomere lengths of 3.5‐4.6 micron to minimize mechanical movement and the related optical artifacts. The over‐all calcium removal capability of each fibre was characterized by analysing the decay of delta[Ca2+] following pulses of several different amplitudes and durations. The rate of sarcoplasmic reticulum (s.r.) calcium release was then calculated for each delta[Ca2+] using the calcium removal properties determined for that fibre. The calculated calcium release wave form reached a relatively early peak and then declined appreciably during a 100‐150 ms depolarizing pulse. The voltage dependence of the peak rate of calcium release was steeper and was centred at more positive membrane potentials than the steady‐state voltage dependence of charge movement in the same fibres. A considerable fraction of the total intramembrane charge was moved at potentials at which delta[Ca2+] and calcium release were only a few per cent of maximum. This 'subthreshold' charge may correspond to charge moved in preliminary transitions that precede a final charge transition that activates release. A 'stepped on' pulse protocol was used to experimentally separate the subthreshold charge movement from the charge movement of the final transitions that may control calcium release. The stepped on pulse consisted of a set 50 ms pre‐pulse to a potential just at or below the potential for detectable delta[Ca2+] followed immediately by a test pulse of varying amplitude and duration. For a wide range of test pulse amplitudes and durations in the stepped on protocol the peak rate of calcium release was linearly related to the charge movement during the test pulse. This result points to a tight control of activation of s.r. calcium release by intramembrane charge movement. The voltage dependence of both charge movement and of the rate of calcium release could be fitted simultaneously with a three‐state, two‐transition sequential model in which charge moves in both transitions but only the final transition activates s.r. calcium release. A model with three identical and independent charged gating particles per channel gave an equally good fit to the data. Both models closely fit the charge movement and release data except within about 10 mV of the voltage at which release became detectable, where release varied more steeply with membrane potential than predicted by either model.(ABSTRACT TRUNCATED AT 400 WORDS)
Non‐cholinergic excitatory and inhibitory junction potentials in the circular smooth muscle of the guinea‐pig ileum.
Authors: Bywater R A , Taylor G S
Published: December 2014

Intracellular micro‐electrodes have been used to record evoked non‐cholinergic junction potentials from the muscle layers of strips of guinea‐pig ileum cut parallel to the longitudinal muscle. Transmural stimulation with single pulses, 0.6 ms duration produced inhibitory junction potentials (i.j.p.s) in the circular muscle layer. In the circular muscle layer, transmural stimulation with repetitive volleys (e.g. three pulses, 0.6 ms, 50 Hz delivered every 4 s) at low stimulus strengths (25‐40 mA) produced non‐cholinergic excitatory junction potentials (e.j.p.s) after an initial i.j.p. At higher stimulus strengths (greater than 40 mA) i.j.p.s occurred following each volley but were superimposed on a prolonged depolarization. Following repetitive volley stimulation every four seconds in the presence of apamin (0.25 microM), the i.j.p.s. were abolished and the non‐cholinergic e.j.p.s clearly showed facilitation. At higher stimulus strengths (and at volley repetition rates of less than 0.1 Hz) volley stimulation now produced an apamin‐resistant slow hyperpolarization followed by a distinct slow depolarization. Electrotonic potentials were readily recorded from the superficially located longitudinal muscle cells: in this muscle layer transmural stimulation produced small, slow changes in membrane potential. These results suggest that non‐cholinergic excitatory and inhibitory nerve fibres primarily supply the circular rather than the longitudinal muscle layer in the guinea‐pig ileum.
Effects of mono and divalent cations on total and partial reactions catalysed by pig kidney Na,K‐ATPase.
Authors: Beaugé L , Campos M A
Published: December 2014

Interactions of Na, K, Ca and Mg ions with partially purified Na,K‐ATPase from pig kidneys were investigated using as a tool simultaneous determinations of adenosine 5'‐triphosphate (ATP)‐adenosine 5'‐diphosphate (ADP) exchange and ATPase activity catalysed by the enzyme. In the presence of 120 mM‐NaCl and 0.5 mM‐MgCl2, the effects 12 mM‐KCl on ATP‐ADP exchange depended on the ATP and ADP concentrations: stimulation (about 10‐fold) with 3 mM‐ATP‐0.75 mM‐ADP, no effect with 0.04 mM‐ATP‐0.01 mM‐ADP and inhibition when ATP and ADP concentrations were 0.003 mM and 0.001 mM respectively. The apparent affinities (K0.5) for K stimulation of ATP‐ADP exchange and Na,K‐ATPase activity were indistinguishable from each other both at 20 mM‐ and 120 mM‐Na. All Na and Na+K‐dependent exchanges were completely abolished by 10(‐4) M‐ouabain. In the absence of K, intermediate Na concentrations were inhibitory of ouabain‐sensitive ATP‐ADP exchange and ATPase activity. This Na inhibition was more pronounced at low than at high ionic strength and was more noticeable in the exchange reaction. K ions antagonized these Na effects; this K‐Na antagonism was more effective on ATPase than on the ATP‐ADP exchange. Ca ions, in the absence of Mg, could sustain ATP‐ADP exchange. Qualitatively the behaviour of the exchange reaction was similar to that observed with Mg. Quantitatively the rates were always lower with Ca. In the presence of Mg, at low ionic strength and at concentrations which stimulated phosphatase activity, Ca ions were not able to counteract Na inhibition of ATPase and ATP‐ADP exchange or to stimulate ATPase activity in the presence of Na. This is another indication of the different reactivity of the K sites involved in phosphatase and ATPase activities as well as of those responsible for the release of Na inhibition of ATPase and exchange reaction. In K‐free solutions containing 0.5 mM‐Na and low ionic strength, Mg was a powerful inhibitor of ouabain‐sensitive ATPase and ATP‐ADP exchange; the curves relating remaining activities to Mg concentrations were identical for both reactions. When Na was increased to 5 mM, ATP‐ADP exchange became more sensitive and ATPase more resistant to Mg inhibition. These data are consistent with (i) a Na‐Mg antagonism at the phosphorylation step, and (ii) a Na‐Mg synergism in blocking the E2PNa‐E1PNa transformation.(ABSTRACT TRUNCATED AT 400 WORDS)
Measurement of intracellular calcium during the development and relaxation of tonic tension in sheep Purkinje fibres.
Authors: Eisner D A , Valdeolmillos M
Published: December 2014

The photoprotein aequorin was micro‐injected into several cells in a sheep Purkinje fibre. The intracellular Ca concentration [( Ca2+]i) was measured from the resulting light emission. Inhibition of the Na‐K pump with strophanthidin resulted in the development of tonic tension which increased on depolarization. This increase was accompanied by an increase of aequorin light. Increasing external Ca concentration [( Ca2+]o) or the magnitude of the depolarization increased both light and tension. If the depolarizing pulse was maintained for several minutes then both tonic tension and aequorin light slowly decayed. The relationship between tension and light was unaffected during this decay. On repolarization the light decayed to below the level before the depolarization before slowly increasing. During this period a test depolarization produced increases of aequorin light and tension which were smaller than control. The application of ryanodine (1‐10 microM) abolished all components of tension other than the tonic component. Under these conditions the time course of the increase of tonic tension and aequorin light on depolarization was sufficiently slow to be measured. In most (five out of six) experiments the relationship between light and tension during this development of tonic tension was found to be similar to that during the subsequent spontaneous decay. However, in one experiment the decay of force was greater than could be accounted for by the fall of [Ca2+]i. It is concluded that most of the spontaneous relaxation of tonic tension can be attributed to a fall of [Ca2+]i rather than to other explanations such as an intracellular acidification or increase of inorganic phosphate concentration.