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Biomedical subjects

R Weingart

Publications and source records attributed to R Weingart.

At least 55 records · Page 3Linked to original sources
PubMed1988

Action potential transfer in cell pairs isolated from adult rat and guinea pig ventricles.

An enzymatic procedure was used to obtain ventricular cells from adult rat and guinea pig hearts. Isolated pairs of cells were selected to study the action potential transfer from cell to cell and determine the resistance of the nexal membrane, rn. For this purpose, each cell of a cell pair was connected to a patch pipette so as to enable whole-cell, tight-seal recording. Normal impulse transmission was observed when rn ranged from 5-265 M omega. In these cases, the action potential in both cells occurred virtually simultaneously. An occasional failure in action potential transfer was seen in cell pairs whose rn had increased to 155-375 M omega. In these cases, the impulse transfer across the nexal membrane occurred with considerable delay. Impulse transfer was completely blocked once rn was larger than 780 M omega. Assuming a single connexon conductance of 100 pS, this would mean that more than 13 connexons are necessary to allow impulse transfer from cell to cell. Two single myocytes, gently pushed together, neither showed electrotonic interaction nor impulse transfer, thus rendering unlikely the possibility of an ephaptic signal transmission.

Action Potentials↗
PubMed1987

Cell-to-cell coupling studied in isolated ventricular cell pairs.

Cell pairs isolated from adult rat and guinea pig ventricles were used to study the electrical properties of the nexal membrane. Each cell of a pair was connected to a voltage-clamp system so as to enable whole-cell, tight-seal recording. The current-voltage relationship of the nexal membrane was found to be linear, revealing a resistance rn of 2-4 M omega. rn was insensitive to the sarcolemmal membrane potential (range: -90 to +30 mV), and exerted no time-dependent gating behavior (range: 0.1 to 10 s). Lowering pHi yielded a small increase in rn. Vigorous elevations in [Ca2+]i gave rise to an increase in rn which was associated with a cell shortening. Uncoupling caused by aliphatic alcohols or halothane did not produce cell shortening. Cell pairs were also used to study action potential transfer.

Action Potentials↗
PubMed1987

Cell pairs isolated from adult guinea pig and rat hearts: effects of [Ca2+]i on nexal membrane resistance.

Cell pairs isolated from adult rat and guinea pig ventricles were used to study the resistance of the nexal membrane, rn. Each cell of a cell pair was connected to a voltage-clamp circuit to obtain simultaneous whole-cell, tight-seal recordings. With this technique, rn was determined under experimental conditions aimed at primarily modifying [Ca2+]i. Moderate changes in [Ca2+]i (produced by trains of depolarizing voltage-clamp pulses activating the slow inward current, or alterations in [Ca2+]o from 0.5 to 10 mM), resulted in no change in rn for normally coupled cell pairs (rn = 5 M omega), but small and reversible changes in slightly uncoupled preparations (rn greater than or equal to 50 M omega). Large increases in rn developed with substantial elevations in [Ca2+]i (secondary to [Na+]o-withdrawal, exposure to strophanthidin in conjunction with isi, or Ca2+-dialysis). Increases in rn brought about via elevation in [Ca2+]i always were accompanied by cell shortening consistent with a sustained contracture. The current-voltage relationship of the nexal membrane was ohmic regardless of whether rn was low (control) or elevated (after increasing [Ca2+]i).

Animals↗
PubMed1986

Electrical properties of the nexal membrane studied in rat ventricular cell pairs.

Cell pairs isolated from adult rat ventricles were used to characterize the electrical properties of the nexal membrane located between the cells. Each cell of a cell pair was connected to a suction pipette so as to enable whole-cell recordings. A double voltage-clamp method was employed which allowed the voltage gradient across the nexal membrane to be controlled. The current-voltage relationship of the nexal membrane was found to be linear over a broad range of transnexal voltages ( +/- 50 mV). The measurements revealed a mean value for the apparent nexal membrane resistance, rn(app), of 3.4 M omega. Taking into account the contribution of an uncompensated series resistance (access resistance), the effective nexal resistance, rn(eff), amounts to 1.7 M omega, approximately. The nexal membrane resistance was found to be insensitive to the sarcolemmal membrane potential, Vm (voltage range tested: -90 mV to +30 mV). The nexal membrane showed no rectifying property, i.e. it allows impulse transmission in both directions equally well. The connexons of the nexal membrane exhibited no time-dependent gating behaviour (time range investigated: 0.1-10 s).

Action Potentials↗
PubMed1985

Electric current flow in cell pairs isolated from adult rat hearts.

Cell pairs were isolated from ventricles of adult rat hearts so as to study cell-to-cell coupling. Both cells of each pair were impaled with micro-electrodes connected to balanced bridge circuits. Rectangular current pulses were passed and the resulting voltage deflexions monitored. The data were analysed in terms of a delta configuration of three resistive elements, the resistances of the non-junctional membrane of cell 1 and cell 2 (rm, 1 and rm, 2), and the resistance of the nexal membrane (rn). The nexal membrane resistance was found to be insensitive to voltage gradients across the non-junctional membrane (range examined: -70 to -10 mV) and direction of current flow. The mean value of rn was 2.12 M omega ([K+]o = 12 mM). Taking into account morphological parameters, this corresponds to a specific nexal membrane resistance (Rn) of 0.1 omega cm2. Spontaneous uncoupling in which one cell remained polarized while the other one depolarized was never observed. The current-voltage relationship of the non-junctional membrane was found to be bell-shaped. The specific resistance (Rm) at the resting membrane potential (approximately -50 mV) was 3.2 k omega cm2 ([K+]o = 12 mM). Comparative studies performed on single cells revealed a similar relationship Rm versus Vm. Rm at the resting membrane potential (Vm approximately -50 mV) was 2.5 k omega cm2 ([K+]o = 12 mM). The specific capacitance of the non-junctional membrane (Cm) was determined from experiments on single cells. Cm was found to be independent of Vm (voltage range: -80 to 0 mV). The mean value of Cm was 1.66 microF/cm2 ([K+]o = 12 mM). For comparison, experiments on cell pairs and single cells were also carried out with [K+]o = 4 mM. The values obtained for Rn, Rm and Cm did not deviate significantly from those found with [K+]o = 12 mM.

Action Potentials↗
PubMed1984

Free calcium in sheep cardiac tissue and frog skeletal muscle measured with Ca2+-selective microelectrodes.

Microelectrodes filled with neutral carrier selective to Ca2+ were used to measure the free intracellular Ca2+ concentration [( Ca2+]i) in sheep cardiac tissue and frog skeletal muscle. Calibration of the electrodes was performed in the presence of a solution resembling the cationic composition of the cytoplasm. [Ca2+]i at rest in normal physiological saline (20-22 degrees C) was 240 nM in Purkinje fibres, 270 nM in ventricular muscle, and 52 nM in skeletal muscle. In Purkinje fibres, elevation of [Ca2+]o from 1.8 mM to 5.4 mM produced a 1.7-fold increase in [Ca2+]i. Elevation of [Ca2+]o from 1.8 mM to 18 mM induced a 2.6-fold increase in [Ca2+]i. Exposure to Na+-free solution (Li+-substituted) gave rise to elevation of [Ca2+]i by factors of 5.8 and 14 in ventricular muscle and Purkinje fibres, respectively. These latter changes in [Ca2+]i were associated with the development of contractures which reached 34% and 172% of the corresponding twitch tension.

Animals↗
PubMed1984

Electric current flow in a two-cell preparation from Chironomus salivary glands.

Conventional micro-electrode techniques were used to study the passive electrical properties of salivary glands from Chironomus nuditarsis insect larvae of the fourth instar stage. Linear cable analysis performed on intact glands revealed the following constants: axial intracellular resistance, Ri = 2730 omega cm; membrane resistance per unit apparent cylindrical area, Rm = 1350 omega cm2; membrane capacitance per unit apparent cylindrical area, Cm = 17.6 microF cm-2. The multicellular glands were reduced to intact two-cell preparations by destroying neighbouring cells mechanically. Each cell of a coupled cell pair was impaled with two micro-electrodes, one to pass rectangular current pulses and the other to monitor the resulting voltage deflexions. Internal consistency tests revealed that the experimental data under steady-state conditions may be described accurately by an equivalent circuit consisting of a delta configuration of three resistive elements: the resistances of the non-junctional membrane of cell 1 and cell 2 (r1 and r2), and the resistance of the gap junctional membrane connecting the two cells (rg). The current-voltage relation of the non-junctional membrane was found ohmic over a membrane potential ranging from -40 mV to + 10 mV. The mean value of Rm was 2020 omega cm2. The resistance function of the gap junctional membrane was also ohmic. There was no dependence of gap junctional resistance on voltage or direction of current flow, at least over the relatively narrow range of potentials tested (approximately +/- 10 mV). Individual values of rg varied from 20 to 3800 k omega, with an over-all mean of 1100 k omega. The lower values are thought to represent the physiological state of cellular coupling, whereas the higher ones may reflect partial uncoupling caused by local damage. The proposed cell pair is a suitable preparation for studying problems related to intercellular coupling.

Animals↗
PubMed1982

Effect of 50% external sodium in solutions of normal and twice normal tonicity on internal sodium activity in frog skeletal muscle.

Neutral carrier based sodium-selective microelectrodes were used to monitor intracellular sodium activity in single frog skeletal muscle fibres during exposure to 50% external sodium solutions at normal and twice normal tonicity. Intracellular sodium activity in normal Ringer was 12.3 +/- 0.7 mM and was increased to 34.4 +/- 1.3 mM in hypertonic solution. Exposure to normotonic or hypertonic solutions containing only 50% sodium (NaCl) replaced by sucrose to maintain tonicity) did not affect the intracellular sodium activity during at least 20 min. Thus, in frog skeletal muscle, external sodium appears not to play a major role in regulating internal sodium, e.g. through ion exchange mechanisms as postulated for other excitable tissues.

Animals↗
PubMed1982

Ungulate cardiac purkinje fibres: the influence of intracellular pH on the electrical cell-to-cell coupling.

1. Passive electrical properties of sheep cardiac Purkinje fibres were assessed by performing linear cable analysis. In a separate set of experiments pH(i) was monitored using recessed-tip pH-sensitive micro-electrodes.2. In Tris-buffered Tyrode solution (nominally CO(2)-free), the pH(i) was 7.27, in bicarbonate-buffered solution equilibrated with 6% CO(2), the mean pH(i) was 7.02.3. Application of 15 mM-NH(4)Cl produced a rapid intracellular alkalinization (0.19 pH units), followed by a slower acidification. Removal of NH(4)Cl gave rise to a slow and transient intracellular acidification (0.5 pH units).4. The biphasic and transient shift in pH(i), induced by the NH(4)Cl treatment, was accompanied by a change of the inside longitudinal resistance per unit fibre length, r(i), displaying a similar time course. The increase in pH(i) produced a maximum decrease in r(i) of 16.4%, while the decrease in pH(i) yielded a maximum increase in r(i) of 30.4%.5. Changing from bicarbonate-buffered Tyrode solution equilibrated with 6% CO(2) to Tris-buffered Tyrode solution led to an increase in pH(i) (0.26 pH units). A subsequent change to bicarbonate-buffered Tyrode solution equilibrated with 15% CO(2) produced a decrease in pH(i) (0.48 pH units). Both changes were sustained.6. This CO(2) protocol gave rise to corresponding changes in r(i); the intracellular alkalosis was associated with a decrease in r(i) (21.2%), and the intracellular acidosis was accompanied by an increase in r(i) (30%).7. Based on recent findings showing an interaction between pH(i) and pCa(i) (Hess & Weingart, 1980), it is concluded that the changes in r(i) are directly caused by protons and not indirectly via secondary changes of the [Ca(2+)](i).8. The pH(i)-dependent changes in r(i) are likely to reflect alterations of the nexal resistance, r(n), because the cytoplasmic resistance, r(c), has the inverse sensitivity to pH(i).9. Unlike pCa(i), pH(i) would seem to be able to modify the cell-to-cell coupling by increasing or decreasing r(i) over a rather narrow range, without ever producing electrical uncoupling.10. Because of basic differences in the action of calcium and protons on the cell-to-cell coupling (magnitude of the effect, operative concentration range), it is tempting to conclude that there is more than one kind of binding site which controls the nexal conductance.

Ammonium Chloride↗
PubMed1982

Free magnesium in sheep, ferret and frog striated muscle at rest measured with ion-selective micro-electrodes.

1. Neutral carrier-based liquid membrane micro-electrodes were constructed which are suitable for continuous measurements of [Mg(2+)](i) in cardiac and skeletal muscle preparations.2. The electrodes show a Nernstian behaviour in pure MgCl(2) solutions. In the presence of a constant ionic background chosen to simulate the cytoplasmic composition, the calibration function flattens progressively with lower [Mg(2+)], due to the interference of K(+) and Na(+). The response to changes in [Mg(2+)] is less than 0.5 sec.3. In quiescent preparations at room temperature (23 degrees C), the following basal [Mg(2+)](i) were determined: 3.5 mM (sheep Purkinje fibres), 3.1 mM (sheep ventricular muscle), 3.0 mM (ferret ventricular muscle) and 3.3 mM (frog skeletal muscle).4. In cardiac tissue, electrical stimulation does not measurably affect the basal [Mg(2+)](i).5. In the presence of 0.5 mM-Mg(2+) (o), the calculated Mg(2+) equilibrium potentials, E(Mg), are in the range of -23 to -25 mV, suggesting that Mg(2+) is not passively distributed across the sarcolemma in striated muscle.6. Further studies were performed on sheep Purkinje fibres to investigate the effect of various experimental interventions on [Mg(2+)](i).7. Elevating [Mg(2+)](o) from 0.5 to 10 mM resulted in a reversible increase of [Mg(2+)](i). The initial rate of increase corresponds to a Mg(2+) influx of 0.42 p-mole/cm(2).sec, or a magnesium permeability, P(Mg), of 1.6 x 10(-8)cm/sec.8. Increasing P(CO) (2) from nominally 0 to 100 mmHg (Tris-buffered vs. bicarbonate-buffered Tyrode solution) produced a reversible decrease in [Mg(2+)](i) by roughly 0.45 mM, probably due to Mg(2+) binding the newly formed intracellular HCO(3) (-).9. The effect of metabolic poisoning on [Mg(2+)](i) was assessed by exposure to cyanide, iodoacetic acid and 2-4-dinitrophenol. No significant increase in [Mg(2+)](i) indicative of a liberation of Mg(2+) from ATP was observed.

Animals↗
PubMed1979

Cellular and subcellular mechanisms of cardiac pacemaker oscillations.

Rhythmic oscillations in the membrane potential of heart cells are important in normal cardiac pacemaker activity as well as cardiac arrhythmias. Two fundamentally different mechanisms of oscillatory activity can be distinguished at the cellular and subcellular level. The first mechanism, referred to as a surface membrane oscillator, can be represented by a control loop in which membrane potential changes evoke delayed conductance changes and vice versa. Since the surface membrane potential is a key variable within the control loop, the oscillation can be interrupted at any time by holding the membrane potential constant with a voltage clamp. This mode of oscillation seems to describe spontaneous pacemaker activity in the primary cardiac pacemaker (sinoatrial node) as well as other regions (Purkinje fibre, atrial or ventricular muscle). In all tissues studied so far, the pacemaker depolarization is dominated by the slow shutting-off of an outward current, largely carried by potassium ions. The second mechanism can be called an internal oscillator since it depends upon a subcellular rhythm generator which is largely independent from the surface membrane. Under voltage clamp, the existence of the internal oscillation is revealed by the presence of oscillations in membrane conductance or contractile force which occur even though the membrane potential is held fixed. The two oscillatory mechanisms are not mutually exclusive; the subcellular mechanism can be preferentially enhanced in any given cardiac cell by conditions which elevate intracellular calcium. Such conditions include digitalis intoxication, high Cao, low Nao, low or high Ko, cooling, or rapid stimulation. Several lines of evidence suggest that the subcellular mechanism involves oscillatory variations in myoplasmic calcium, probably due to cycles of Ca uptake and release by the sarcoplasmic reticulum. The detailed nature of the Cai oscillator and its interaction with the surface membrane await further investigation.

Animals↗
PubMed1978

Role of calcium ions in transient inward currents and aftercontractions induced by strophanthidin in cardiac Purkinje fibres.

1. Under the influence of strophantidin, Purkinje fibres exhibit transient inward current (TI) which contributes to arrhythmogenic activity. Voltage-clamp experiments were carried out to study the role of Ca ions in this phenomenon. 2. The amplitude of TI varied directly with the extracellular Ca concentration, CaO. Magnesium ions had an antagonistic effect. 3. TI was closely associated with a phasic increase in force ("aftercontraction"). Like TI, the aftercontraction was evoked by a preceding action potential or by the break of a strong depolarizing pulse. 4. TI and the aftercontraction displayed similar wave forms although peak current preceded peak force by 50--100 msec. Both transients were enhanced by increasing the strength or duration of the preceding depolarization pulse. Both events were slowed as the potential level following the pulse was displaced in the negative direction. 5. TI and the aftercontraction could be evoked in the absence of cardiotonic steroids by strongly elevating CaO. 6. Additional experiments were carried out to test the hypothesis the TI reflects an influx of Ca2+ ions. Moninhibited TI but the developed and removal of the inbibition lagged far behind the effects on the slow inward current. 7. TI could be suppressed and eventually inverted by varying the membrane potential in the positive direction. The inversion potential averaged -5mV and was not consistent with a Ca-specific pathway. The aftercontraction was more closely related to the phasic conductance change underlying the current than to thecurrent flow itself. 8. The results are consistent with the idea that an oscillatory release of Ca from an intracellular store is the primary event underlying both the aftercontraction and the conductance change which generates TI. Digitalis intoxication or very high CaO may promote such events by elevating intracellular Ca levels.

Animals↗
PubMed1978

Ionic basis of transient inward current induced by strophanthidin in cardiac Purkinje fibres.

1. Voltage clamp experiements studied the ionic basis of the strophathidin-induced transient inward current (TI) in cardiac Purkinje fibres. 2. The reversal potential of TI (Erev) was determined in the presence of various bathing solutions. Erev averaged --5 m V in the standard modified Tyrode solution (Kass, Lederer, Tsien & Weingart, 1978). Erev was displaced toward more negative potentials when the external Na concentration (NaO) was reduced by replacement of NaCl with Tris Cl, choline Cl or sucrose. 3. A sudden reduction of NaO evoked a temporary increase in TI, followed after a few minutes by a sustained diminution. The initial increase was closely paralleled by an enhanced aftercontraction and could be explained by an indirect effect of NaO on internal Ca. The subsequent fall in TI amplitude could be accounted for by the reduced driving force, E--Erev. 4. Erev was not significantly changed by replacing extracellular Cl with methyl-sulphate, or by limited variations in external Ca (2.7--16.2 mM) or external K (1--8 MM). 5. These results are consistent with an increase in membrane permeability to Na and perhaps K. 6. TI was not directly affected by TTX, which blocks excitatory Na channels, or by Cs, which inhibits inwardly rectifying K channels. TI may be distinguished from the slow inward current by its kinetic, pharmacological and ionic properties. 7. TI might be carried by a pre-existing ionic pathway such as the 'leak' channel which provides inward current underlying normal pace-maker depolarization. Another possibility is that TI reflects Ca extrusion by an electrogenic Ca--Na exchange.

Animals↗
PubMed1977

The actions of ouabain on intercellular coupling and conduction velocity in mammalian ventricular muscle.

1. The effects of ouabain on the electrical coupling between cells and the conduction velocity, theta, were studied in ventricular muscle preparations from calf and cow hearts using a silicon-oil-chamber. 2. After 90 min of exposure to 2 X 10(-6) M ouabain, an increase of the inside longitudinal resistance, Ri, from 420 omega cm to 1032 omega CM was observed. Assuming a constant myoplasmic resistivity this presumably reflects a reduced electrical coupling between myocardial cells. 3. Concomitantly, theta was decreased from 50-3 to 29-4 cm/sec. This change could be explained by the observed alterations in the maximal rate of rise of the action potential, (dV/dt)max, the amplitude of the action potential Vp, the membrane capacity Cf, and the sum, respectively, of the inside and outside longitudinal resistance per unit distance (ri + ro). Quantitatively, about 60% of the decrease of theta could be accounted for by the experimentally determined increase of Ri. 4. Time course studies revealed a biphasic action of ouabain on Ri. An early dose-dependent drop in Ri, equivalent to an improvement of the intercellular coupling, was followed by a delayed massive increase in Ri, whose onset and magnitude were also concentration-dependent. 5. The delayed increase in Ri was associated with an increase of the diastolic tension. Toxic ouabain doses (2 X 10(-6) M) produced irreversible changes on both parameters, whereas thereapeutic doses (less than 5 X 10(-7) M) affected neither of them. Reversible effects on both parameters were observed at an intermediate drug concentration (10(-6) M). 6. The strong correlation between decoupling and contracture is consistent with the idea that the intracellular Ca concentration, [Ca]i, is involved in the control of the nexal conductance. This is supported by the finding that increasing the extracellular Ca concentration, [Ca]o, accelerated the ouabain-induced decoupling, whereas reducing [Ca]o retarded it. 7. If anything, the contracture slightly preceded the increase in Ri. From this it is concluded that the threshold [Ca]i for the electrical decoupling between cells must be somewhat larger than the threshold level for the tension activation. 8. The delayed increase in Ri is compatible with an inhibition of the Na pump which according to the Na-lag hypothesis predicts an increase of [Ca]i secondary to a Na-accumulation. The early drop in Ri can either be explained by a stimulation of the Na pump, or by a non-monotonic relationship between Ri and [Ca]i.

Action Potentials↗
PubMed1976

Inotropic effect of cyclic AMP in calf ventricular muscle studied by a cut end method.

1. Cyclic AMP was introduced into ventricular muscle by a cut-end method. Trabecular bundles were pulled through a partition which divided the preparation into a loading region and a test region. The loading region was exposed to Ca-free solution, cut transversely near the partition, and then briefly exposed to cyclic AMP. The test region was continually superfused with Tyrode soltuion. 2. In preliminary experiments, cell-to-cell movements were studied in long bundles by including [3H]cyclic AMP in the loading procedure and allowing redistribution to occur. After suitable test periods, the bundles were removed, frozen, and sliced into segments. Segment radioactivity was plotted against distance and fitted by a theoretical diffusion curve. 3. The results showed longitudinal redistribution of label over many cell lengths with an average effective diffusivity of 8 X 10(-7) cm2/sec. This value did not appear sensitive to the length of the test period or to the presence of a phosphodiesterase inhibitor. 4. The metabolic fate of cyclic AMP introduced by the cut-end method was determined by chromatographic separation of [3H]cyclic AMP and its break-down products. Most of the cyclic AMP was metabolized, but the results suggest that cell-to-cell movements of cyclic AMP contribute to the overall redistribution of label. 5. The cut-end method was used to study the influence of cyclic AMP on the contractile activity in the test region. Introduction of cyclic AMP evoked a delayed increase in twitch tension, about 25% above control. The inotropic effect peaked about 50 min after the end of the loading procedure, a delay which seemed compatible with slow longitudinal diffusion into the test region. 6. In control experiments, the cut-end procedure was repeated with 5'AMP (the immediate break-down product of cyclic AMP) instead of cyclic AMP. No delayed increase in twitch tension was observed. 7. Introduction of dibutyryl cyclic AMP increased twitch amplitude by 130%, with a delayed time course similar to that found for cyclic AMP. 8. The results using the cut-end procedure provide new evidence that cyclic AMP helps mediate adrenergic effects on the strength of contraction.

Action Potentials↗