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R E Ten Eick

Publications and source records attributed to R E Ten Eick.

At least 37 records · Page 2Linked to original sources
PubMed1988

Evidence for two components of sodium channel block by lidocaine in isolated cardiac myocytes.

The effects of lidocaine on sodium current in cardiac myocytes isolated from cat and guinea pig were investigated using the whole-cell variation of the patch-clamp technique. Lidocaine (43-200 microM) reduced sodium current during repetitive depolarizing pulses in a use-dependent manner. To clarify the nature of the use-dependent block, we characterized the time course of block development using a two-pulse protocol. Two distinct phases of block development were found: a rapid phase (tau = 1-6 msec) having a time course concurrent with the time course of channel activation, and a slower phase (tau = 100-900 msec), which developed after channels inactivated. The amplitude of the block during the rapid phase of development was a steep function of transmembrane voltage over the range of -70 to +20 mV. The voltage-dependence was similar to that for sodium channel activation (sodium conductance) but was too steep to be attributed solely to the passive movement of a singly charged molecule under the influence of the transmembrane voltage gradient. These results suggest that use-dependent block of sodium channels in cardiac tissue may result from an interaction of lidocaine with sodium channels in the activated as well as the inactivated channel states. Possible mechanisms underlying the fast component of block are discussed.

Action Potentials↗
PubMed1986

Characterization of a sodium pump-induced hyperpolarization in isolated human atrium.

Specimens of right atrial appendage from 106 patients were incubated in cold Tyrode solution, and transmembrane resting potentials (Em) were recorded during rewarming at selected temperatures. Rewarming caused a transient hyperpolarization to develop. The hyperpolarization had a temperature threshold between 17 and 22 degrees C and was inhibited by acetylstrophanthidin. Acetylcholine (ACh) induced a depolarization during early rewarming in 7, 10, 20, and 40 mM K+, indicating that Em hyperpolarized to a potential negative to the equilibrium potential for K+. ACh had no effect after some decline of Em, and hyperpolarization was induced by ACh when Em had reached steady state. The relationship between [K+] in the bulk phase of the superfusate [( K]b) and the "reversal potentials" for the ACh effect was log linear and had a slope of 61.7 mV per tenfold change in [K]b. The relationship between [K]b and hyperpolarization was studied in the presence of 0.5 mM Ba2+. The apparent [K]b resulting in half-maximal pump-induced hyperpolarization was 1.3 mM. The data indicate that human atrium can pump Na+ electrogenically and that the characteristics of the Na+ pump-induced hyperpolarization resemble those described for cardiac tissue from several other mammalian species.

Aged↗
PubMed1985

Inhibition of electrogenic Na-pumping attributable to binding of cardiac steroids to high-affinity pump sites in human atrium.

Binding of cardiac steroids to the Na,K-pump may occur at both high- and low-affinity sites. Binding at low-affinity sites causes pump inhibition. However, the functional significance of binding at high-affinity sites is controversial. The effects of cardiac steroids presumed bound at high-affinity sites on electrogenic Na-pumping was therefore examined in human atrial tissue. Specimens were preloaded with Na+ by cooling to 2 degrees C for 60 min and then rewarmed to 30 degrees C in 20 mM K+. In nine control experiments, the resting membrane potential hyperpolarized to -69.9 +/- 0.7 mV (mean +/- S.E.) due to enhanced Na,K-pump activity upon rewarming. Maximal hyperpolarization was less negative during exposure to 10(-9) to 10(-6) M acetylstrophanthidin in a dose-dependent manner. The differences between maximal hyperpolarization during control experiments and during exposure to acetylstrophanthidin were attributed to pump inhibition. Inhibition occurred at all acetylstrophanthidin concentrations including the low range in which binding at high-affinity sites should predominate. The relationship between acetylstrophanthidin concentration and pump inhibition was bimodal with a "shoulder" around 10(-8) M. The data were well described by a model which assumes that acetylstrophanthidin binds at both low capacity-high-affinity (half-saturation, 3.9 X 10(-9)M) and high capacity-low-affinity sites (half-saturation, 4.8-6.1 X 10(-7) M). Nonlinearity in the experimental assay of pump function did not appear to explain the bimodal concentration-inhibition relationship. Thus, cardiac steroids may cause Na,K-pump inhibition in humans by binding to high-affinity pump sites.

Acetylcholine↗
PubMed1984

Characterization of the block of sodium channels by phenytoin in mouse neuroblastoma cells.

The interaction of phenytoin (DPH) with membrane ionic channels of cultured N1E-115 neuroblastoma cells was studied. The single suction pipette technique was used for voltage clamp and intracellular perfusion. When the cells were held at -80 mV for periods of 1 min or more, DPH (20-100 microM) inhibited inward sodium current in a dose-dependent manner (resting block); resting block was relieved by hyperpolarizing cells to -100 mV for 1 min. A hyperpolarizing shift of the slow inactivation curve for the Na current was induced by DPH and can explain the effect of holding potential on the resting block. The fast Na inactivation curve, however, was not affected. During repetitive pulsing the DPH-induced inhibition of Na current was enhanced (conditioned block). Conditioned block was both voltage- and frequency-dependent. Conditioning pulses to potentials which do not appreciably open Na channels also produced conditioned block; prolongation of conditioning pulses even to durations longer than the time for maximal steady-state inactivation of the Na current progressively increased the extent of conditioned block, suggesting that DPH can interact with inactivated and closed Na channels. The time course of recovery from voltage-dependent inactivation of sodium current during conditioned block was both slowed and exhibited voltage dependence. Recovery occurred faster when membrane potential during the recovery period was more negative. We conclude that DPH blocks Na channels both by increasing the fraction of channels in an inactivated state and by delaying the transition from inactivated to closed but available channels. This effect is enhanced by depolarizing membrane potential and increasing the frequency of stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1983

On the mechanism of lysophosphatidylcholine-induced depolarization of cat ventricular myocardium.

Lysophosphatidylcholine, a putative biochemical mediator of ischemia-induced arrhythmias, reduces the resting potential of ventricular muscle. To elucidate possible mechanisms of lysophosphatidylcholine-induced depolarization, we investigated the effects of lysophosphatidylcholine on the electrophysiological properties of cat ventricular muscle, using potassium ion-selective electrodes and conventional microelectrode, current-, and voltage-clamp techniques. Lysophosphatidylcholine (50 microM) decreased the sensitivity of the resting potential to changes in extracellular potassium concentration. Hyperpolarization of lysophosphatidylcholine-depolarized fibers by current-clamp methods failed to reveal two stable levels of resting potential. Depolarizing concentrations of lysophosphatidylcholine did not reduce the potassium equilibrium potential, as determined from the reversal potential of the time-dependent potassium current and measurements of intracellular potassium activity using potassium ion-selective electrodes. Lysophosphatidylcholine induced a depolarizing shift of the reversal potential for steady state current, and did not induce the formation of a negative slope region in the steady state current-voltage or background current-voltage relationships. Lysophosphatidylcholine induced an inward shift and linearization of the background current-voltage relationship negative to -30 mV, and the lysophosphatidylcholine-sensitive component of the background current was an inward rectifier with a reversal potential approximately equal to the potassium equilibrium potential. Lysophosphatidylcholine also reduced the amplitudes of the time-dependent potassium current, slow inward current, and the potassium accumulation and depletion currents. These results indicate that lysophosphatidylcholine-induced depolarization is due, in part, to reduced potassium conductance at voltages near the normal resting potential, and that lysophosphatidylcholine may act as a nonspecific depressant of membrane channels.

Action Potentials↗
PubMed1981

Autonomic nervous system and cellular injury from circumflex ligation in dogs.

The role of the autonomic nerves in the development of irreversible cellular injury (ICI) after circumflex coronary occlusion was examined in dogs with intact, acutely, or chronically decentralized cardiac nerves. Cardiac nerves were chronically decentralized 2 wk before ligation (CD) or acutely at the time of ligation (AD). In one group of AD dogs, the beta-blocker oxprenolol (0.3 mg/kg) was administered before ligation (AD + Ox). Hearts were paced at 160 beats/min to exclude any contribution of rate change secondary to autonomic intervention. The results are expressed in terms of percent of the cross-sectional area of the posterior papillary muscle (PPM) sustaining ICI after 40-min occlusion: intact 64 +/- 4% (SE), 6 +/- 4%, AD 39 +/- 10%, and AD + Ox 2 +/- 2%. Both acute and chronic denervation protect against ICI even in the absence of changes in heart rate. Furthermore, in dogs with intact cardiac nerves, reduction in pacing rate from 160 to 60 beats/min also decreased the extent of ICI from 64 +/- 4 to 34 +/- 10%. Experiments defining the time course of development of ICI in the PPM indicate that protection was only temporary, delaying the onset of injury by 25 min. These findings suggest that 1) neural activity in extrinsic cardiac sympathetic nerves activate beta-receptors, thereby influencing the development of ICI, and 2) differences in protection afforded by acute denervation with and without beta-blockade indicated that intrinsic postganglionic sympathetic nerve terminals can liberate transmitter in response to ischemia even in the absence of extrinsic neural activity.

Animals↗
PubMed1977

Depletion and accumulation of potassium in the extracellular clefts of cardiac Purkinje fibers during voltage clamp hyperpolarization and depolarization: experiments in sodium-free bathing media.

Voltage clamp hyperpolarization and depolarization result in currents consistent with depletion and accumulation of potassium in the extracellular clefts o cardiac Purkinje fibers exposed to sodium-free solutions. Upon hyperpolarization, an inward current that decreased with time (id) was observed. The time course of tail currents could not be explained by a conductance exhibiting voltage-dependent kinetics. The effect of exposure to cesium, changes in bathing media potassium concentration and osmolarity, and the behavior of membrane potential after hyperpolarizing pulses are all consistent with depletion of potassium upon hyperpolarization. A declining outward current was observed upon depolarization. Increasing the bathing media potassium concentration reduced the magnitude of this current. After voltage clamp depolarizations, membrane potential transiently became more positive. These findings suggest that accumulation of potassium occurs upon depolarization. The results indicate that changes in ionic driving force may be easily and rapidly induced. Consequently, conclusions based on the assumption that driving force remains constant during the course of a voltage step may be in error.

Animals↗
PubMed1975

Effect of beta receptor blockade on the initiation and perpetuation of ouabain-induced ventricular tachyarrhythmia.

The role of the cardiac beta receptor in the genesis and perpetuation of ouabain-induced ventricular tachyarrhythmias (VT) was investigated in the chloralose (20 mg/kg)-urethane (200 mg/kg) anesthetized dog. This was achieved by determining: 1) the effect of oxprenolol (0.3 mg/kg), a potent beta receptor blocking agent possessing no significant direct membrane effects on the myocardium, on the dose of ouabain necessary to cause VT (i.e., the toxic dose); and 2) whether oxprenolol had antirrhythmic efficacy against preexisting VT. The toxic dose was determined by giving a bolus injection of ouabain (similar to 36 mug/kg) plus a subsequent ouabain infusion (similar to 0.40 mug/kg min-minus 1) until VT occurred. VT was defined as at least one-third of the ventricular beats being of ectopic ventricular origin. The existence of an effective beta receptor blockade was verified by showing that 0.75 mug/kg of isoproterenol (an ED50 dose) injected intravenously had no detectable cardiovascular effects. The results were: 1) oxprenolol (0.3 mg/kg) did not alter the toxic dose significantly (P greater than .5 for both paired and group comparisons) [63.9 plus or minus 2.3 (S.E.) mug/kg vs. 64.4 plus or minus 2.9 (S.E.) mug/kg]; and 2) attempts to convert VT to sinus rhythm with oxprenolol (0.3 mg/kg) failed in 20 of 21 trials. Oxprenolol (1.0 mg/kg) effected only a temporary [10.6 plus or minus 6.4 (S.D.) minutes] reversion to sinus rhythm in 10 of 21 attempts. These results indicate that an activation of the cardiac beta receptor is not prerequisite for either the initiation or the perpetuation of ouabain-induced ventricular tachyarrhythmia in this particular model. The results cannot provide support for the notion that an increase in cardiac sympathetic nerve activity is a principal factor in VT in the dog. However, the results are consistent with the hypothesis that the direct membrane actions of ouabain are a principal cause of ouabain-induced ventricular tachyarrhythmia.

Adrenergic beta-Antagonists↗