bluuebunny/crossref_metadata_2025 huggingface dataset:
The kinetics of recovery and development of potassium channel inactivation in perfused squid (Loligo pealei) giant axons.
Authors: Chabala L D
Published: December 2014

K+ currents were studied at a normal (‐69 mV) and at a depolarized (‐49 mV) membrane potential in voltage‐clamped squid giant axons perfused with 350 mM‐K+ and bathed in K+‐free artificial sea water containing tetrodotoxin to block the Na+ channels. Steady‐state and instantaneous K+ currents were reduced by over 50% at corresponding voltages at the depolarized membrane potential. Instantaneous chord conductance‐voltage curves showed that the depolarized membrane potential caused a uniform reduction of K+ conductance across the voltage range under study. The driving force for K+ ions was comparable at both membrane potentials when a short (2 ms) pre‐pulse was used to open the K+ channels. When a longer (7.5 ms) pre‐pulse was used, the driving force was actually larger at the depolarized membrane potential. The depolarized membrane potential did drive some K+ ions into the periaxonal space. The amount of K+ ions driven into the periaxonal space was estimated by two independent methods, with similar results. The resulting increase of K+ ions in the periaxonal space (10 mM) was about 40 times too small to account for the large reduction in currents in terms of a reduced driving force for K+ ions. The kinetics of recovery and development of inactivation were monitored by repeatedly applying a 7.5 ms test pulse followed by a long conditioning potential. Both recovery and development of inactivation, from the depolarized membrane potential, were described by the sum of two exponential terms plus a constant. The time constant‐voltage curves for both phases of inactivation peaked at about ‐54 mV at 10 degrees C. The time constant of the slow phase of inactivation at ‐54 mV was about 12.4 s, while the corresponding time constant for the fast phase was about 2.3 s. The slow relaxation had an apparent plateau of about 11 s at more depolarized membrane potentials. Recovery from inactivation was rapid at hyperpolarized membrane potentials. The steady‐state inactivation curve of the K+ channel was incomplete in the depolarizing region; and apparent plateau was reached with about 75% of the K+ current inactivated. The temperature sensitivity of both phases of inactivation corresponded to a Q10 of about 3. Elevated external concentrations of K+ ions did not block either phase of the inactivation process, although the kinetics of recovery from inactivation were slightly faster under these conditions.(ABSTRACT TRUNCATED AT 400 WORDS)
Mutual entrainment and electrical coupling as mechanisms for synchronous firing of rabbit sino‐atrial pace‐maker cells.
Authors: Jalife J
Published: December 2014

The mechanisms of synchronous firing of cardiac pace‐makers were studied using thin (0.3‐0.5 mm) rabbit sino‐atrial (s.a.) node strips placed in a three‐compartment tissue bath. Superfusion of the central segment (1 mm in length) with ion‐free sucrose solution permitted the electrical insulation of the external segments and the development of two independent pace‐maker 'centres': one fast (F); one slow (S). An external shunt pathway was used to modulate the degree of coupling between F and S. Superfusion of the central segment with Tyrode solution containing heptanol (3.5 mM) instead of sucrose induced progressive decrease in the amplitude of responses in this segment and led to progressive loss of F:S synchronization. Eventually the two pace‐makers became totally independent from each other. These changes were reversible upon wash‐out of heptanol. When a pace‐maker centre was within the range of influence of local circuit (i.e. electronic) currents from the pace‐maker in the opposite side of the sucrose (or heptanol) compartment, its period was prolonged or abbreviated, depending on phase and frequency relations. Dynamic F:S interactions at various degrees of electrical coupling resulted in mutual entrainment with both pace‐makers beating at simple harmonic (i.e. 1:1, 2:1, 1:2, etc.) or more complex (3:2, 5:4, etc.) ratios that depended on the degree of coupling and the intrinsic periods of the individual pace‐maker centres. The patterns of synchronization could be predicted by the phasic sensitivity of each pace‐maker to brief electrotonic inputs. The results suggest that when two individual pace‐maker cells are connected through low resistance junctions, the period resulting from their mutual entrainment should be a function of their respective intrinsic frequencies, their phase relations and the degree of electrical coupling. The data further suggest that the heart beat is initiated by a 'democratic' type of synchronous firing of cells in the s.a. node, with each pace‐maker cell contributing to an aggregate signal and involving mutual entrainment between cells.
Does the sympathetic nervous system influence sinus arrhythmia in man? Evidence from combined autonomic blockade.
Authors: Coker R , Koziell A , Oliver C , Smith S E
Published: December 2014

The influences of vagal and sympathetic efferent activity on sinus arrhythmia in man have been studied in healthy subjects by administration of hyoscine butylbromide and atenolol alone and combined using a microcomputer‐linked electrocardiogram (e.c.g.) system. Sinus arrhythmia was quantitated as the S.D. of the R‐R interval. Sinus arrhythmia was reduced by hyoscine butylbromide, in some subjects to near abolition, but this end‐point was unchanged by pre‐treatment with atenolol. Atenolol alone prolonged the mean R‐R interval and increased sinus arrhythmia. It is suggested that sinus arrhythmia in man is mediated through vagal efferents alone but that atenolol increases the arrhythmia through a central vagotonic effect.
Corrective reactions to stumbling in man: neuronal co‐ordination of bilateral leg muscle activity during gait.
Authors: Berger W , Dietz V , Quintern J
Published: December 2014

Electromyogram (e.m.g.) responses of lower leg muscles, and corresponding movements were studied following a perturbation of the limb during walking, produced by either (a) a randomly timed, short acceleration or decelerating impulse applied to the treadmill, or (b) a unilateral triceps surae contraction induced by tibial nerve stimulation. Bilateral e.m.g. responses following the perturbation were specific for the mode of perturbation and depended on the phase of the gait cycle in which the perturbation occurred. Treadmill deceleration evoked a bilateral tibialis anterior activation; acceleration evoked an ipsilateral gastrocnemius and contralateral tibialis anterior activation (latency in either condition and on both sides was 65‐75 ms, duration about 150 ms). Tibial nerve stimulation at the beginning of a stance phase, was followed by an ipsilateral tibialis anterior activation; during the swing phase it was followed by an ipsilateral tibialis anterior and contralateral gastrocnemius activation (latency about 90 ms, duration about 100 ms). These patterns differed from the response seen after a unilateral displacement during static standing, which evoked a bilateral tibialis anterior activation. These early responses were in most cases followed by late ipsilateral responses, but the e.m.g. pattern of the next step cycle was usually unchanged, or affected only at its onset. The e.m.g. responses were unaltered by ischaemic nerve blockade of group I afferents, by training effects or by pre‐warning of the onset of perturbation (randomly or self‐induced). Despite the different e.m.g. responses following a perturbation during gait, the same basic functional mechanism was obviously at work: the early ipsilateral response achieved a repositioning of the displaced foot and leg, while the early contralateral and late ipsilateral responses provided compensation for body displacement. It is suggested that the e.m.g. responses may be mediated predominantly by peripheral information from group II and group III afferents, which modulate the basic motor pattern of spinal interneuronal circuits underlying the respective motor task.
Total cytoplasmic calcium in relaxed and maximally contracted rabbit portal vein smooth muscle.
Authors: Bond M , Shuman H , Somlyo A P , Somlyo A V
Published: December 2014

The concentration of total cytoplasmic Ca in vascular smooth muscle was measured by electron probe microanalysis of strips of rabbit portal anterior mesenteric vein that were rapidly frozen either when relaxed or during a maintained (30 min) maximal contraction stimulated with high K and noradrenaline. Strips were also frozen and analysed after incubation in Ca‐free, high‐Mg2+ solution. Probe diameters of 0.1‐0.2 micron and 1.0‐1.5 micron were used to measure, respectively, cytoplasmic and cellular (including stored) Ca. There was a highly significant increase (P less than 0.0005) in cytoplasmic Ca of 1.0 +/‐ 0.2 (S.D.) mmol Ca/kg dry wt. from 0.8 +/‐ 0.2 (S.E. of mean) mmol/kg dry wt. (n = 262 spectra, six animals) to 1.8 +/‐ 0.2 (S.E. of mean) mmol Ca/kg dry wt. (n = 296 spectra, six animals), during maximal contraction. This increase is greater than can be accounted for by Ca binding to calmodulin and to myosin, suggesting the presence of other Ca‐binding proteins in smooth muscle. A small amount (0.4‐0.6 mmol/kg dry wt.) of cytoplasmic Ca remained after incubation in Ca‐free, high‐Mg2+ EGTA solution. This tightly bound, cytoplasmic Ca is insufficient to account for the total amount of divalent cation known to be bound to F‐actin. We conclude that Mg is the major inexchangeably bound cation in F‐actin in smooth as in striated muscle. In the contracted muscles, the cellular Ca concentration, measured with the large probes that include Ca stored in the sarcoplasmic reticulum (s.r.), was 3.2 +/‐ 0.3 (S.E. of mean) mmol Ca/kg dry wt. (n = 93), significantly higher than the cytoplasmic Ca concentration measured with small probes. This value of cellular Ca is probably an underestimate, as the large‐diameter probes did not cover all of the peripheral s.r. The cellular Ca (measured with large probes) was highest in the contracted and lower in the relaxed tissue, and was significantly reduced in the muscles incubated in Ca‐free solution. In contracted muscle, cytoplasmic Mg significantly decreased and mitochondrial Mg increased. In 0 Ca, high‐Mg2+ solution, the cytoplasmic Mg increased significantly. Mitochondrial Ca did not significantly change during a maintained contraction, but was significantly lower (0.0 +/‐ 0.2 (S.E. of mean) mmol Ca/kg dry wt.) after incubation in Ca‐free, high‐Mg2+ solution than in the relaxed tissue (1.6 +/‐ 0.2 mmol Ca/kg dry wt.) in normal Ca‐containing solution.
Spatial and temporal contrast sensitivities of neurones in lateral geniculate nucleus of macaque.
Authors: Derrington A M , Lennie P
Published: December 2014

The discharges of single neurones in the parvocellular and magnocellular laminae of the macaque's lateral geniculate nucleus (l.g.n.) were recorded with glass‐insulated tungsten micro‐electrodes. Linearity of spatial summation was examined using the test devised by Hochstein & Shapley (1976). 2 of 272 parvocellular units and 6 of 105 magnocellular units showed clearly non‐linear spatial summation. A quantitative index of non‐linearity did not suggest the existence of a distinct 'non‐linear' class of magnocellular unit. Spatial contrast sensitivity to moving gratings was measured by a tracking procedure in which contrast was adjusted to elicit a reliable modulation of discharge. With the exception of cells that were driven by blue‐sensitive cones, measurements of contrast sensitivity did not reveal distinct subgroups of parvocellular units. All had low sensitivity, and those with receptive fields in the fovea could resolve spatial frequencies of up to 40 cycles deg‐1. Magnocellular units had substantially higher sensitivity, but poorer spatial resolution. The higher sensitivities of magnocellular units led to their giving saturated responses to stimuli of high contrast. Responses of parvocellular units were rarely saturated by any stimulus. At any one eccentricity the receptive fields of parvocellular units had smaller centres than did those of magnocellular units. Receptive fields of magnocellular units driven by the ipsilateral eye had larger receptive fields than did those driven by the contralateral eye. Parvocellular units were most sensitive to stimuli modulated at temporal frequencies close to 10 Hz; magnocellular units to stimuli modulated at frequencies nearer 20 Hz. The loss of sensitivity as temporal frequency fell below optimum was more marked in magnocellular than parvocellular units. Changes in temporal frequency altered the shapes of the spatial contrast sensitivity curves of both parvocellular and magnocellular units. These changes could be explained by supposing that centre and surround have different temporal properties, and that the surround is relatively less sensitive to higher temporal frequencies.
Chromatic mechanisms in lateral geniculate nucleus of macaque.
Authors: Derrington A M , Krauskopf J , Lennie P
Published: December 2014

This paper introduces a new technique for the analysis of the chromatic properties of neurones, and applies it to cells in the lateral geniculate nucleus (l.g.n.) of macaque. The method exploits the fact that for any cell that combines linearly the signals from cones there is a restricted set of lights to which it is equally sensitive, and whose members can be exchanged for one another without evoking a response. Stimuli are represented in a three‐dimensional space defined by an axis along which only luminance varies, without change in chromaticity, a 'constant B' axis along which chromaticity varies without changing the excitation of blue‐sensitive (B) cones, a 'constant R & G' axis along which chromaticity varies without change in the excitation of red‐sensitive (R) or green‐sensitive (G) cones. The orthogonal axes intersect at a white point. The isoluminant plane defined by the intersection of the 'constant B' and 'constant R & G' axes contains lights that vary only in chromaticity. In polar coordinates the constant B axis is assigned the azimuth 0‐180 deg, and the constant R & G axis the azimuth 90‐270 deg. Luminance is expressed as elevation above or below the isoluminant plane (‐90 to +90 deg). For any cell that combines cone signals linearly, there is one plane in this space, passing through the white point, that contains all lights that can be exchanged silently. The position of this 'null plane' provides the 'signature' of the cell, and is specified by its azimuth (the direction in which it intersects the isoluminant plane of the stimulus space) and its elevation (its angle of inclination to the isoluminant plane). A colour television receiver was used to produce sinusoidal gratings whose chromaticity and luminance could be modulated along any vector passing through the white point in the space described. The spatial and temporal frequencies of modulation could be varied over a large range. When stimulated by patterns of low spatial and low temporal frequency, two groups of cells in the parvocellular laminae of the l.g.n. were distinguished by the locations of their null planes. The null planes of the larger group were narrowly distributed about an azimuth of 92.6 deg and more broadly about an elevation of 51.5 deg, which suggests that they receive opposed, but not equally balanced, inputs from only R and G cones. These we call R‐G cells.(ABSTRACT TRUNCATED AT 400 WORDS)
Is there more than one circadian clock in humans? Evidence from fractional desynchronization studies.
Authors: Folkard S , Minors D S , Waterhouse J M
Published: December 2014

Three groups of four healthy volunteers lived in an isolation unit for 24 days. During this time they lived by a clock which, unknown to themselves, ran progressively faster so that, by real time, the 'day' decreased from 24.0 to 22.0 h in length. Throughout this protocol, the subjects lived a regular regimen of sleep, waking and meals based upon their 'local' time clock. They collected regular urine samples that were analysed for a variety of constituents. Rectal temperature was also recorded automatically throughout. The effects of such a protocol upon circadian rhythmicity in these variables were investigated by a variety of techniques including cosinor analysis. The results showed that the temperature rhythm was less able to adjust to a shortening 'day' than were the urinary variables, with the possible exception of potassium; that is, the protocol forced an internal desynchronization to exist between different variables. These results are discussed in terms of both the possibility that more than one internal circadian clock might exist and the direct effect that sleep exerts upon the expression of circadian rhythms.
The sarcomere length dependence of the rate of heat production during isometric tetanic contraction of frog muscles.
Authors: Elzinga G , Peckham M , Woledge R C
Published: December 2014

Heat production and force have been measured as a function of sarcomere length between 1.6 and 3.0 microns during isometric tetani at 0 degree C for two types of frog muscle: sartorius and extensor longus digiti iv (e.l.d. iv). Stable heat rate declines linearly with increasing sarcomere length above 2.20 microns for both e.l.d. iv and sartorius muscles. In sartorius muscle stable heat rate remains at or near its maximum value between 1.75 and 2.20 microns while force decreases. In e.l.d. iv muscle, both stable heat rate and force decline linearly as sarcomere length decreases below 2.20 microns.
Alteration of cytoplasmic ionized calcium levels in smooth muscle by vasodilators in the ferret.
Authors: Morgan J P , Morgan K G
Published: December 2014

Aequorin was used as an indicator of cytoplasmic Ca2+ levels during the action of vasodilators in potassium‐depolarized strips of ferret portal vein. Moderate concentrations of isoprenaline produced either no change or an increase in cytoplasmic Ca2+ levels during smooth muscle relaxation. Only in the presence of very high concentrations of isoprenaline (greater than 10(‐4) M) was a decrease in intracellular Ca2+ levels detectable. Both papaverine and forskolin also caused relaxations of the muscle while cytoplasmic Ca2+ levels were observed either not to change or to increase. When the muscles were relaxed either by decreasing the calcium concentration in the bathing medium or by the addition of sodium nitroprusside, light and force fell together. The ratio of force to light was greater when the muscle was relaxed with calcium depletion than with the addition of sodium nitroprusside, indicating that sodium nitroprusside was relaxing the muscle by more than just decreasing cytoplasmic Ca2+ levels. These results indicate that not all vasodilators cause a lowering of cytoplasmic Ca2+ levels and indicate that, in intact cells, agents associated with increases in cytoplasmic cyclic AMP levels can cause an uncoupling of calcium‐force relations.
Adrenomedullary function in the neonatal rat: responses to acute hypoxia.
Authors: Seidler F J , Slotkin T A
Published: December 2014

The mechanism of release of catecholamines from the adrenal medulla of neonatal rats was examined, together with the role of these amines in the ability of the organism to withstand acute O2 deprivation. Splanchnic innervation of the rat adrenal is non‐functional until the end of the first postnatal week. Nevertheless, hypoxia caused depletion of adrenal catecholamines in 1‐day‐old rats as well as in 8‐day‐old animals. Pre‐treatment with cholinergic receptor blocking agents did not prevent the catecholamine response at 1 day but did in older animals; these results indicate that the depletion mechanism is not neurogenic in 1‐day‐old animals but is neurogenic in 8‐day‐old animals. The proportions of noradrenaline and adrenaline released by hypoxic stress also differed at the two ages, with preferential release of adrenaline by the neurogenic mechanism but not by the non‐neurogenic one. The ontogenetic replacement of non‐neurogenic adrenomedullary responses by the neurogenic mechanism was directly related to the onset of splanchnic nerve function. Treatments which accelerated the development of neuronal connexions (neonatal hyperthyroidism, maternal stress) caused premature loss of the non‐neurogenic response. Prior to the development of sympathetic nerve function, adrenal catecholamines plays a predominant role in enabling the neonate to survive hypoxia. Interference with the release of adrenal amines invariably increased mortality during hypoxia. In contrast, interference with sympathetic neural release of catecholamines did not affect the ability of 1‐day‐old rats to withstand hypoxia, indicating that survival during low PO2 conditions is not dependent on the sympathetic innervation at that stage of development. After functional development of the sympathetic nerves and disappearance of non‐neurogenic adrenomedullary responses, the neonatal rats became partially dependent upon catecholamines derived from sympathetic terminals; administration of bretylium at 8 days significantly compromised survival during hypoxia. Interference with adrenergic receptor function also interfered with the ability of neonatal rats to withstand low PO2. At 1 day of age, either phenoxybenzamine or ICI‐118551, but not atenolol, shortened the survival time during hypoxia. At 8 days, only phenoxybenzamine did so.(ABSTRACT TRUNCATED AT 400 WORDS)
The effects of oestrogens on spontaneous activity and responses to phenylephrine of the mammalian urethra.
Authors: Callahan S M , Creed K E
Published: December 2014

The electrical and mechanical activity of strips of urethral smooth muscle from female ovariectomized rabbits were studied. Results were compared with strips from guinea‐pigs, dogs and Tammar wallabies and with anaesthetized rabbits. From pressure recordings in intact animals and contractile responses of strips it was concluded that in the urethra of the rabbit both cholinergic and alpha‐adrenergic receptors were excitatory. Urethral strips from rabbits and wallabies had continuous spontaneous mechanical activity that was reduced by pre‐treatment with oestrogen. In dogs spontaneous activity was transient and in guinea‐pigs was usually absent. The alpha‐adrenergic agonist, phenylephrine, produced a dose‐related contraction of urethral strips from all species. Pre‐treatment with oestrogen produced no significant change in the rabbit and guinea‐pig but increased sensitivity in the dog and wallaby. Electrical activity was recorded with micro‐electrodes from smooth muscle cells of rabbit and guinea‐pig urethra. In both species pre‐treatment with oestrogen produced slight depolarization. In rabbits regular spike activity was recorded from all animals but there was a tendency for double spikes and reduced amplitude following oestrogen treatment. In guinea‐pigs bursts of spikes occurred in control animals; after hormone treatment there was often incomplete recovery of spikes within the burst. The results indicate that oestrogens can influence the smooth muscle of the urethra by modifying both spontaneous activity and the responses to stimulation of alpha‐adrenoceptors.
Currents carried by monovalent cations through calcium channels in mouse neoplastic B lymphocytes.
Authors: Fukushima Y , Hagiwara S
Published: December 2014

Membrane currents through the Ca2+ channel were studied in a hybridoma cell line (MAb‐7B) constructed by fusion of S194 myeloma cells and splenic B lymphocytes from the mouse. The whole‐cell variation of the patch‐electrode voltage‐clamp technique was used. When [Ca2+]o = 2.5 mM, [Na+]o = 150 mM and [Na+]i = 155 mM, the current reversed from inward to outward at 20.9 +/‐ 2.4 mV (mean +/‐ S.D., n = 62). Both inward and outward currents showed voltage‐dependent inactivation with the same membrane potential dependence of steady‐state inactivation. The decay time constant of the current decreased from about 27 ms at ‐44 mV to a saturation value of 16 ms at about ‐20 mV, and remained at this value even when the current became outward. From the above results both the inward and outward currents were considered to flow through Ca2+ channels. The inward current showed no change when the external Na+ was replaced with Cs+ or tetraethylammonium and increased when [Ca2+]o was increased. Also, the reversal potential became more positive with increasing [Ca2+]o with a slope of 29 mV/decade change of [Ca2+]o. Effects of different divalent cations examined at 10 mM concentration showed the reversal potential to become more positive in the order of Mn2+, Sr2+ approximately equal to Ba2+ and Ca2+ whereas the relative maximum amplitudes of peak inward current were 1.0 for Ca2+, 1.24 for Sr2+, 0.99 for Ba2+ and 0.07 for Mn2+. When [Ca2+]o or [Mg2+]o was reduced by chelators, monovalent cations became capable of carrying inward current through the Ca2+ channel. These monovalent currents share common kinetic properties with the Ca2+ current, as judged from the steady‐state inactivation and the decay time constant of the current. The monovalent cation current was blocked by divalent cations in a voltage‐dependent manner. The half‐blocking concentrations of Ca2+ and Mg2+ at ‐45 mV were 2.0 X 10(‐6) M and 3.0 X 10(‐5) M respectively. The same voltage‐dependent binding mechanism can explain the outward current carried by monovalent cations at large positive potentials at normal Ca2+ concentrations. The suppression of the monovalent currents by Ca2+ and Mg2+ showed different voltage dependences. The suppression by Ca2+ increased and then decreased as the membrane potential was made negative, whereas the suppression by Mg2+ increased monotonically. This difference can be explained by considering the fact the Ca2+ is permeant and Mg2+ is impermeant through the Ca2+ channel.
Transient responses of coronary flow in the blood‐perfused isolated rat heart submitted to changes in oxygen content.
Authors: Duruble M , Duvelleroy M , Gauduel Y , Martin J L , Teisseire B
Published: December 2014

This study examines the transient response of coronary blood flow to acute changes in O2 content at normal and high arterial PO2 (Pa, O2) in the blood‐perfused, working isolated rat heart. The perfusion system used in this study presents the following advantages: it eliminates the gas/blood interface, includes a peripheral circulation for control of pre‐load and after‐load, and allows for rapid change of perfusates and continuous recording of aortic and coronary blood flow. With this system the isolated rat heart is capable of stable haemodynamic performance for periods in excess of 4 h. A sudden decrease in O2 content from 0.147 to 0.067 11(‐11) at constant Pa,O2 (133 mmHg; n = 15) was associated with a marked increase in coronary blood flow (QCOR). This increase showed two phases: a rapid phase which reached 200% of the control value in 20 s, followed by a slow phase (235% in 90 s). When the same decrease in O2 content (0.135 to 0.057 11(‐1] was associated with an increase in Pa, O2 (n = 22; 143 to 412 mmHg), the response of QCOR was limited both in amplitude (175% rather than 235%) and in rate of onset (response time of 15.6 instead of 9.2 s). These results are consistent with the majority of currently popular hypotheses regarding control of QCOR including the adenosine hypothesis and that of vessel wall PO2 being a direct mediator. The time course of changes in coronary vascular resistance, with a Pa, O2‐dependent rapid phase, suggests the simultaneous function of the two mechanisms.
Apical membrane potassium and chloride permeabilities in surface cells of rabbit descending colon epithelium.
Authors: Wills N K
Published: December 2014

The apical membranes of surface cells in the rabbit descending colon possess a significant ionic conductance in parallel to amiloride‐blockable Na+ channels. The identity of the ion(s) responsible for the amiloride‐insensitive conductance is unknown. The purpose of the present paper was to assess the permeability and net driving forces for K+ and Cl‐ across this membrane using conventional and ion‐sensitive micro‐electrode techniques. Intracellular Cl‐ activity (aiCl) averaged 23 +/‐ 2 mM with an equilibrium potential (ECl) of ‐38 +/‐ 2 mV. This value is less than previous estimates of the electromotive force (e.m.f.) of the amiloride‐insensitive pathway (ca. ‐50 mV). Consequently, Cl‐ alone cannot account for the amiloride‐insensitive conductance. Replacement of Cl‐ by gluconate in the serosal solution decreased aiCl to 17 +/‐ 2.8 mM. aiCl was lowered to approximately 1 mM by replacement in the mucosal bath or by replacement in both solutions. The results indicate a low Cl‐ conductance in the basolateral membrane, in agreement with previous electrophysiological studies of this epithelium. In contrast to Cl‐, the chemical driving force for K+ was large enough to support the e.m.f. of the amiloride‐insensitive pathway (K+ equilibrium potential, EK = ‐66 mV). The basolateral membrane potential (Vbl), EK and the intracellular K+ activity (aiK) were decreased in parallel following inhibition of the basolateral Na‐K pump, providing evidence that Vbl is largely due to a K+ diffusion potential. In the presence of serosal 10(‐4) M‐ouabain, aiK appeared to remain above equilibrium and more than doubled after addition of Ba2+ to the serosal bath. Replacement of the mucosal bathing solution with KCl or gluconate Ringer solution largely restored Vbl and the transepithelial potential (VT) in tissues which had been previously treated with ouabain. The restoration of VT was decreased and the transepithelial resistance (RT) was increased by addition of tetraethylammonium to the mucosal bath. The above results suggest that there are at least four routes for ion movement across the apical membrane of rabbit colon surface epithelial cells. These are: (1) an amiloride‐sensitive Na+ channel, (2) a K+ conductance, (3) electroneutral uptake of Cl‐ from lumen to cell interior and (4) an active K+ transport mechanism, also from lumen to cell interior.
Some properties of the circular myometrium of the sheep throughout pregnancy and during labour.
Authors: Parkington H C
Published: December 2014

Spontaneous electrical and mechanical activity were measured in strips of circular myometrium, stretched to in vivo length, obtained from ewes during pregnancy and parturition. The resting tension was high (280 mN/mm2) early in pregnancy and decreased gradually during the course of gestation to reach low levels (20 mN/mm2) during labour. Strips showed continuous electrical and mechanical activity up to around day 50 of pregnancy. The variability in the amplitude of the action potentials, the occurrence of many small fluctuations in membrane potential and the short space constant (0.9 mm) could be explained by impaired conduction in these tissues. During the second half of pregnancy, muscle strips showed regular bursts of spike activity and contractions with a frequency of about 4/min. The space constant (lambda) increased gradually to around 2 mm at term. The membrane time constant (tau m) remained constant at approximately 130 ms throughout gestation. Tissues from ewes in labour were not spontaneously active but action potentials could be evoked by depolarizing current pulses. The space constant increased to 4.6 +/‐ 0.4 mm and tau m increased to 510 +/‐ 50 ms at this time. Verapamil (10(‐6) M) rapidly abolished electrically evoked activity in strips obtained from ewes in labour. Verapamil abolished spontaneous activity in strips from animals up to day 145 of pregnancy, though a higher concentration (2 X 10(‐5) M) was required. However, action potentials could be evoked by depolarizing current pulses and these were accompanied by contractions that were 50‐80% of those observed in control solution. Cobalt (2mM) had an effect on spontaneous and electrically induced activity that was similar to that of verapamil. The threshold for the initiation of an action potential was increased in all tissues in the presence of the blockers. Verapamil decreased lambda by about 50% in the later stages of pregnancy and during labour. During labour alone verapamil reduced tau m by about 50%. These results show that the onset of labour in the ewe is associated with rapid and dramatic changes in both the passive and active properties of the circular muscle of the uterus.
Electrical properties of rat dorsal root ganglion neurones with different peripheral nerve conduction velocities.
Authors: Harper A A , Lawson S N
Published: December 2014

The electrical characteristics of individual rat dorsal root ganglion neurones were studied and related to the peripheral axon conduction velocity and morphological cell type. Neurones were divided into four groups based on the conduction velocity of their peripheral axons (A alpha, 30‐55 m/s; A beta, 14‐30 m/s; A delta, 2.2‐8 m/s and C less than 1.4 m/s). Electrophysiological parameters examined included membrane potential, action potential amplitude and duration, after‐potential height and duration, input resistance and the occurrence of time‐dependent rectification. The mean duration of the somatic action potentials was found to be characteristic for each of the conduction velocity groupings. However, there was considerable overlap between groups. The fast‐conducting (A alpha) and slowly conducting (A delta) myelinated fibres had short‐duration action potentials, within the ranges 0.49‐1.35 and 0.5‐1.7 ms at the base respectively. The A beta and C cells had somatic action potentials with durations in the ranges of 0.6‐2.9 and 0.6‐7.4 ms respectively. The longer action potential durations could be related to the presence of an inflexion on the repolarizing phase seen in a third of A beta neurones (called A beta I neurones) and in all C neurones. The action potential overshoot was larger in C neurones and A beta I neurones than in the other neurone groups. The mean duration of the after‐hyperpolarization was several times greater in C neurones than in A neurones. A delta neurones displayed the shortest and greatest amplitude after‐hyperpolarizations. Large, long‐lasting after‐hyperpolarizations were not limited to neurones displaying an inflexion. The electrophysiological properties of the soma membrane of A delta neurones closely resembled those of A alpha neurones, while in several respects those of C neurones resembled the A beta I neuronal properties. The input resistance was found to be much greater in C than in A cells, although there was no significant difference between specific membrane resistance values calculated for the different groups. A number of A cells exhibited time‐dependent rectification.
Inward rectification in the transverse tubular system of frog skeletal muscle studied with potentiometric dyes.
Authors: Ashcroft F M , Heiny J A , Vergara J
Published: December 2014

The non‐penetrating potentiometric dyes NK2367 and WW375 were used to investigate the effect of inward rectification on the weighted‐average tubular membrane potential in single frog muscle fibres voltage clamped using a three‐Vaseline‐gap method. In 100 mM‐K solution, when inward rectification was activated by hyperpolarization the steady‐state amplitude of the transverse tubular system (T‐system) optical signal was reduced, and its rise time was faster than that recorded for an equivalent depolarization. The voltage dependence of the optical attenuation followed that of inward rectification, increasing with increasing hyperpolarization. For a voltage‐clamp step of ‐140 mV the optical attenuation was 0.72 which corresponds to a weighted‐average T‐system potential change of 100 mV. When inward rectification was blocked in a Cs, TEA solution the optical attenuation was also abolished. The voltage dependence of the block of the inward currents in solutions containing low concentrations of Cs was also reflected in the T‐system optical signals. Our results were satisfactorily predicted by a radial cable model of the T‐system, assuming the same specific inward rectifier conductance in surface and tubular membranes. This analysis predicts that the measured optical attenuation corresponds to a decrease in the tubular space constant, lambda T, from 120 micron under passive conditions to about 40 micron when inward rectification is fully, activated. The voltage dependence of inward rectification measured at the surface membrane was reasonably well predicted by assuming that the specific conductance obeyed a Boltzmann type of voltage dependence; the major effect of tubular decrements was to reduce the steepness of the total (surface + T‐system) conductance‐voltage relation.
Partial neuromuscular blockade and cardiovascular responses to static exercise in man.
Authors: Leonard B , Mitchell J H , Mizuno M , Rube N , Saltin B , Secher N H
Published: December 2014

In human subjects sustained static contractions of the quadriceps femoris in one leg were performed with the same absolute and the same relative intensity before and after partial neuromuscular blockade with either decamethonium or tubocurarine which reduced strength to about 50% of the control value. During the contractions performed with the same absolute force, the magnitude of the cardiovascular responses (heart rate and blood pressure) was greater during neuromuscular blockade than during control contractions. During the contractions involving the same relative force the magnitude of the cardiovascular responses was almost the same with and without neuromuscular blockade. These findings were independent of the drug used. The metabolic part of the exercise pressor reflex was assessed by the application of an arterial cuff 1/2 min before cessation of exercise and for the following 3 min of rest. Although heart rate and blood pressure decreased after cessation of exercise, application of the tourniquet resulted in higher post‐exercise values and this effect was seen both with and without neuromuscular blockade. Muscle biopsies from the subjects' m. vastus lateralis were analysed for fast‐ and slow‐twitch fibre composition showing 27‐66% slow‐twitch fibres. No correlation was found between cardiovascular responses to static exercise, with or without neuromuscular blockade, and fibre type predominance. The results suggest that the involvement of fast‐ or slow‐twitch muscle fibres does not play a dominant role in the cardiovascular responses to static exercise in man. Both central command and reflex neural mechanisms are of importance, and it appears that these two control mechanisms are redundant and that neural occlusion may be operative. However, when partial neuromuscular blockade induces a disproportion between an increase in central command and a constant or decreasing muscle tension and metabolism, the larger signal arising from central command determines the magnitude of the cardiovascular responses.
Neurophysiology and pharmacology of long‐term potentiation in the rat sympathetic ganglion.
Authors: Briggs C A , Brown T H , McAfee D A
Published: December 2014

Brief tetanic stimulation of the preganglionic nerve induced a persistent potentiation of nicotinic synaptic transmission in the rat superior cervical sympathetic ganglion. Quantitative measurements of the post‐tetanic increase in synaptic efficacy revealed two distinct time courses. The early, rapidly decaying component, termed post‐tetanic potentiation (p.t.p.), had a decay time constant of 2‐3 min, as reported elsewhere. The duration of the more persistent component, called long‐term potentiation (l.t.p.), was extremely temperature dependent, lasting much longer at 32 degrees C than at 22 degrees C. In half of the experiments performed at 32 degrees C, l.t.p. showed no detectable decay over the course of 1 h or more after a brief tetanic stimulation. Other experiments were conducted at 22 degrees C. The induction of l.t.p. was dependent on the extracellular [Ca2+]. Transient elevation of the extracellular [K+] also produced a long‐term enhancement of synaptic efficacy, and this effect was also Ca2+ dependent. The tetani that were effective in inducing l.t.p. (5‐20 Hz for 5‐20 s) were well within the physiological range of preganglionic activity. The magnitude and time course were related to frequency and duration of stimulation. The occurrence of l.t.p. was restricted to those preganglionic fibres that were tetanically stimulated. This lack of heterosynaptic or generalized effects was demonstrated by splitting the preganglionic nerve into two branches that could be independently tested and conditioned. Physiological activation of muscarinic or nicotinic receptors apparently does not play an essential role in causing ganglionic l.t.p., which is expressed as an enhancement of nicotinic transmission. A muscarinic antagonist (2 microM‐atropine) did not block l.t.p. Preganglionic stimulation induced l.t.p. even when a high concentration of a nicotinic antagonist (3 mM‐hexamethonium) was present during the tetanic stimulation. Furthermore, bath application of a cholinergic agonist (100‐1000 microM‐carbachol) could not substitute for tetanic stimulation in provoking l.t.p. Activation of adrenergic receptors also appeared not to play an essential role. Neither a beta‐adrenergic antagonist (10 microM‐sotolol or 1 microM‐propranolol) nor an alpha‐adrenergic antagonist (1 microM‐phentolamine) had any significant effect on the magnitude or duration of l.t.p. The results indicate that ganglionic l.t.p. is a Ca2+‐ and temperature‐dependent process that can be created independently of the activation of nicotinic, muscarinic or adrenergic receptors.
Voltage and ion dependences of the slow currents which mediate bursting in Aplysia neurone R15.
Authors: Adams W B , Levitan I B
Published: December 2014

The previous paper described a slow depolarizing tail current, ID, and a slow hyperpolarizing tail current, IH, that are activated by action potentials and by brief depolarizing pulses in Aplysia neurone R15. ID and IH are necessary for the generation of bursting pace‐maker activity in this cell. In this paper, the voltage and ion dependence of ID and IH are studied in an effort to determine the charge carriers for the two currents. When the slow currents are activated by brief depolarizing pulses delivered under voltage clamp in normal medium, an increase in the size of the pulse of 5‐10 mV is usually sufficient to bring about full activation of ID. The apparent threshold in normal medium is approximately ‐20 mV. In medium in which K+ channels are blocked, full activation of an inward tail current that resembles ID requires increasing the pulse amplitude by only 1‐2 mV. In contrast, IH is activated in a graded fashion over a 40 mV range of pulse amplitudes. After activating the currents with action potentials or with supramaximal pulses, ID remains an inward current and IH an outward current over a range of membrane potentials spanning ‐20 to ‐120 mV. In normal medium, ID is dependent on both extracellular Na+ concentration ( [Na+]o) and extracellular Ca2+ concentration ( [Ca2+]o). When K+ channels are blocked, ID can be supported by either [Na+]o or [Ca2+]o. IH depends only on [Ca2+]o as long as [Na+]o is at least 50 mM. Neither ID nor IH is decreased by decreasing the K+ gradient or by application of K+ channel blockers. These treatments increase somewhat the apparent amplitude of ID, probably by unmasking it from the large K+ tail current that follows the depolarizing pulse. A direct comparison in the same cell of the tetraethylammonium sensitivity of IH and of the Ca2+‐activated K+ current demonstrates that these two currents flow through separate and distinct populations of channels. We conclude that in R15, ID arises in response to the triggering of an axonal action potential which in turn, through an as yet unknown mechanism, causes an increased influx of Na+ and/or Ca2+. We conclude that the apparent outward current IH, which is responsible for the interburst hyperpolarization in a normally bursting R15, in fact arises from a decrease in a resting inward Ca2+ current, possibly as the result of Ca2+‐induced inactivation of Ca2+ channels.
Lateral filamentary spacing in chemically skinned murine muscles during contraction.
Authors: Matsubara I , Umazume Y , Yagi N
Published: December 2014

A mouse toe muscle was chemically skinned with saponin and the 1,0 spacing of the hexagonal myofilament lattice at a sarcomere length of 2.5 micron was measured with the X‐ray‐diffraction method. In the relaxed state, the 1,0 spacing was 40.8 nm. When the muscle was maximally activated at pCa 4.4, the spacing decreased to 38.4 nm. During contractions at lower calcium concentrations, the spacing decreased less. In rigor, the spacing decreased to almost the same extent as during maximum contraction, although the rigor tension was only 8% of the maximum tension. When the spacing in relaxed muscle had been adjusted osmotically to about 38 nm, activation caused no further decrease in the spacing. The results support the view that the force responsible for the lattice shrinkage during contraction is produced by cross‐bridges displaced from their optimum lateral positions.
Enhancement of long‐term potentiation in the rat dentate gyrus by post‐trial stimulation of the reticular formation.
Authors: Bloch V , Laroche S
Published: December 2014

The possibility that post‐trial stimulation of the mesencephalic reticular formation (m.r.f.) may modulate long‐term potentiation (l.t.p.) at the perforant path to dentate granule cell synapses was studied in freely moving rats. Extracellular potentials evoked in the dentate gyrus by test pulses to the perforant path were recorded before and at various delays after a series of high‐frequency stimulus trains to the perforant path (ten trains of eight pulses at 400 Hz, delivered at 5 min intervals). We have compared the magnitude and duration of l.t.p. of the population spike in this control condition with that observed when a low‐intensity m.r.f. stimulation was delivered 10 s after each train to the perforant path. Post‐event m.r.f. stimulation enhanced the amount of l.t.p. induced by the series of high‐frequency stimulus trains and prolonged its duration for several days. The size of the population spike was unaffected by repeated m.r.f. stimulation in the absence of perforant path high‐frequency stimulation, or when this failed to induce significant l.t.p. The temporal gradient of efficacy of m.r.f. stimulation was investigated. M.r.f. stimulation delivered 10 s after a single high‐frequency stimulation of perforant path fibres resulted in an enhanced l.t.p. of both the population excitatory post‐synaptic potential (e.p.s.p.) and population spike. L.t.p. was unaffected by m.r.f. stimulation given either before, or 120 s after perforant path high‐frequency stimulation. These results show that low‐intensity m.r.f. stimulation enhances lasting changes in synaptic function in the dentate gyrus when delivered during a critical period following high‐frequency activation of perforant path fibres. These results are discussed in the light of our previous findings on the effects of post‐event m.r.f. stimulation on memory and on the development of associative changes in hippocampal multiunit activity during conditioning. It is hypothesized that l.t.p.‐like mechanisms may be involved in the stabilization of neural networks by experience and that this process might be reinforced by diffuse m.r.f. activation.