PubMed Health⌕ Search

Biomedical subjects

A I Undrovinas

Publications and source records attributed to A I Undrovinas.

At least 37 records · Page 2Linked to original sources
PubMed1989

Ischemic poison lysophosphatidylcholine modifies heart sodium channels gating inducing long-lasting bursts of openings.

The effects of lysophosphatidylcholine (LPC) on Na channels in inside-out patches of adult rat ventricular cells using the patch-clamp technique have been investigated. Application of LPC (9-25 microM) from the inner side of membrane for 4-15 min caused a reduction of averaged Na current (INa) peak and prolonged the time course of inactivation in the potential range of -50 to -10 mV. Analysis of single channel behaviour revealed that after 30-50 min of exposure, in addition to normally functioning Na channels with short openings, LPC induced long-lasting bursts of Na channel openings (up to the 300 ms duration of the test pulses). This resulted in an appearance of noninactivated component of INa. The slope conductance of these modified channels remained the same as in control (11.3 pS - control; 11.6 pS - LPC-treated). The dwell time for modified channels increased significantly.

Animals↗
PubMed1989

Ethacizin blockade of calcium channels: a test of the guarded receptor hypothesis.

The effect on calcium channels of the sodium channel antagonist, ethacizin, was studied in isolated frog ventricular cells using the whole cell voltage-clamp methodology. Ethacizin was found to block inward calcium current in a frequency-, voltage-, and concentration-dependent manner. The frequency-dependent blocking properties were modeled by considering the drug interaction with a voltage-dependent mixture of calcium channels harboring either an accessible or an inaccessible binding site. With repetitive stimulation, the pulse-to-pulse reduction in peak current is shown to be exponential, with a rate linearly related to the interstimulus interval and the drug concentration. Observed frequency- and concentration-dependent blocks were consistent with the predictions of the model, and mixture-specific rate constants were estimated from these data. The negligible shift in channel inactivation and the reduction of apparent binding and unbinding rates with more polarized membrane potentials imply the active moiety of ethacizin blocks open channels and is trapped within the channel at resting membrane potentials. The binding rate at 0 mV is similar to that observed in studies of interactions of other open channel blocking agents with voltage- and ligand-gated channels.

Animals↗
PubMed1989

[Asymmetrical changes in electrical activity of Purkinje fibers and muscle cells after administration of BAY K 8644. A new model of cardiac arrhythmia].

The effects of calcium current agonist BAY K 8644 on transmembrane potential of guinea pig papillary muscle (PM) and sheep Purkinje fibers (PF) were studied. The action potentials (AP) and contractions (C) were recorded. C both of PM and PF increased (two-four times) in response to BAY K 8644 (0.5-5 microM) addition. The AP duration of PM increased slightly (20%) while PF AP duration increased progressively with the time even at low BAY K 8644 dose (0.5 microM). At 5th min, early afterdepolarizations (EAD) occurred. After 10 min drug application PF became inexcitable at high plateau level. TTX and ethmozin (1 microM) restored AP. Thus, changes in ionic currents balance in PF towards the increase in inward calcium current by BAY K 8644 resulted in additional steady state potential at plateau level. The latter might induce EAD and re-entry around functionally inexcitable PF. The similarity of mechanisms of arrhythmias induced by ischemia with the presented model is discussed.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1989

Single channel sodium current in rat cardiomyocytes: use-dependent block by ethacizin.

Ethacizin is a phenothiazine derivative antiarrhythmic agent that blocks sodium current. The cell-attached patch clamp of single adult rat ventricular cells was used to investigate mechanisms of use-dependent block of sodium current. Under control conditions peak open probability, first latency, fraction of null sweeps, mean open time and single channel current amplitude were not different at both 1 and 4 Hz. Ethacizin (5 microM) caused a significant decrease in the peak open probability, a significant increase in the first latency and an increase in the fraction of null sweeps at 4 Hz compared with 1 Hz; mean open time and single channel current amplitude were unchanged. These observations support a model of antiarrhythmic action which proposes complete block of single channel conductance resulting from drug binding. A "runs analysis" revealed nonrandom clustering of null traces in the presence of ethacizin and no clustering in control patches. Increasing stimulation frequency makes this nonrandom behavior more apparent. We conclude that the relatively slow cycling of a few channels between blocked and unblocked states induces null sweeps clustering. The implications of these findings for mechanisms of drug block of the Na channel are discussed.

Animals↗
PubMed1988

Some mechanisms of nonspecific antiarrhythmic action of phosphocreatine in acute myocardial ischemia.

Using isotope-labeled microspheres (diameter 15 microns) it was shown that phosphocreatine at a dose of 300 mg/kg does not affect the myocardial blood flow in the ischemic zone during acute occlusion (5 min) of the left anterior descending coronary artery (LAD) in dogs. Intravenous administration of NaCl hypertonic solution which contained the same amount of Na+ as 300 mg/kg of phosphocreatinine disodium salt prevented the development of ventricular fibrillation during acute LAD occlusion in dogs. Under these conditions excitation conduction velocity significantly increased. Experiments in isolated intraventricular rabbit septum have showed that the addition of phosphocreatine or phosphocreatinine to the perfusion medium at a concentration of 10 mmole/liter increased excitation conduction velocity in ischemic myocardium. However, when changes in perfusate Na+ and Ca2+ concentration produced by addition of phosphocreatine or phosphocreatinine were compensated, these compounds do not affect excitation conduction velocity. On the other hand, the alterations similar to those produced by the addition of phosphocreatine or phosphocreatinine led to the same increase of excitation conduction velocity. The results obtained indicate an important role of the changes of blood plasma ionic composition on intravenous administration of phosphocreatine in electrophysiological and antiarrhythmic effects of this substance during acute myocardial ischemia.

Acute Disease↗
PubMed1988

Use-dependent block of sodium current by ethmozin in voltage-clamped internally perfused canine cardiac Purkinje cells.

Block of sodium current (INa) by ethmozin (moricizine), an antiarrhythmic drug, was investigated in isolated, voltage-clamped, canine cardiac Purkinje cells. Initial block of INa by ethmozin (2 microM) in noninactivated cells (held at -150 mV) was 9.3 +/- 1.2% (S.D.). Additional "use-dependent" block developed in response to repetitive depolarization. This block was both frequency-dependent and dose-dependent with the fall in peak INa greater at increasing depolarization frequencies (0.625 to 4 Hz) and with increasing dose (2 microM to 20 microM). Use-dependent block was modeled according to the guarded receptor hypothesis assuming ingress to the channel binding site during the open state of the channel, and egress from the channel independent of the kinetic state of the channel. The rate constants (on-rate = 2100 +/- 100 (S.D.)/M/ms and off-rate = 1.7 +/- 0.3 (S.D.) 10(-5)/ms) were used to predict the time course of INa block in response to repeated depolarizations and the dose-response relationship of steady-state used-dependent block measured in independent experiments. We conclude that ethmozin blocks INa in Purkinje cells in both a non-use-dependent and a use-dependent manner and that the guarded receptor model is useful in describing the use-dependent block.

Animals↗
PubMed1988

[Study of the nonspecific effect of phosphocreatine disodium salt on the process of excitation conduction in acute myocardial ischemia].

The effect of phosphocreatine and phosphocreatinine disodium salts on excitation conduction in acute myocardial ischemia was investigated, using repeated short-term ischemia exposures of the isolated rabbit ventricular septum as a model. Considerable improvement of excitation conduction through ischemized myocardium, seen after the administration of phosphocreatine and phosphocreatinine salts, was shown to be associated with Na+ added to the perfusion medium. Phosphocreatine and phosphocreatinine effects on excitation conduction time and the septal force in control perfusion were related to both the addition of Na+ and the binding of Ca2+ by these agents in the perfusion medium.

Acute Disease↗
PubMed1987

Electrophysiologic aspects of moricizine HCl.

Moricizine HCl, a phenothiazine derivative, is a new antiarrhythmic drug that has quinidine-like effects on the myocardium. Moricizine HCl, 1 X 10(-7) g/ml, significantly decreases Vmax of the transmembrane action potential of canine Purkinje fibers and reduces the duration of the action potential at 50% and 90% of repolarization, whereas resting potential is unchanged. The drug decreases the fast inward sodium current (lNa), as measured by the double sucrose gap technique in frog atrium trabeculae; the processes of activation, inactivation and reactivation of current did not change even when a high concentration of drug (5 X 10(-6) g/ml) was used. At the same dose, the slow inward calcium current (lCa) increased, but the total outward current did not change. Using the patch-clamp technique, it was shown that moricizine HCl, 1 X 10(-4) g/ml, did not alter single-channel conductance, but essentially decreased the mean open tonic and open-state probability of potassium channels either at positive or negative holding potentials. lNa measured in a single myocyte preparation decreased faster when drug was administered in the external bath compared with intracellular injection. Moricizine HCl action on lNa of the single cell and on Vmax of the action potential is frequency dependent. When lNa was recorded directly, there was a cumulative effect of drug. Similar to other quinidine-like agents, moricizine HCl enhanced arrhythmogenicity within the first few minutes after coronary artery occlusion, but prevented arrhythmias 24 hours after acute myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1987

[Frequency-dependent blocking of single Na channels of cardiomyocytes with ethmozin].

Using a "patch-clamp" technique in "cell-attached" configuration, frequency-dependent blocking of single Na channels in the rat cardiomyocyte membrane with ethmozin was studied. It has been established that blocking effect of ethmozin on the integral sodium current in cardiac cellular membranes at increased stimulation frequency (from 1 to 5 Hz) was associated with the reduced likelihood of the existence of open Na channels. The patency of individual channels remained unchanged.

Animals↗
PubMed1986

[Effect of ethmozin on the electrophysiologic parameters of Purkinje cells in the sheep heart. The frequency-dependent blockade of sodium channels].

The effect of ethmozin (E) on action potential (AP) duration (ADP90, APD50), AP upstroke velocity (Vmax) and cable properties (Ri, Rm, Rin, Cm, lambda m, tau m) was studied. Vmax was significantly reduced by E (0.2 to 5 mkM). Duration of AP plateau (APD50) was more sensitive to E than APD90. Thus, application of 0.5 mkM E resulted in 30% decrease of APD90 and 60% of APD50. This suggested that E not only inhibits INa, what is reflected by Vmax reduction, but also can affect other currents involved in plateau phase. Cable properties remained unchanged in the wide concentration range of E. Blockade of Vmax by E was use-dependent. Uptake rates of ethmozin by sodium channel for different stimulation frequencies were estimated and kinetic binding and unbinding constants (k = 40322 M-1 ms-1; 1 = 7.17 X 10(-5) ms-1) with unguarded receptor were calculated using novel drug-channel interaction model (Starmer and Grant, 1985).

Action Potentials↗
PubMed1984

[Na-Ca-exchange as a mechanism regulating spontaneous contractions of isolated individual cardiomyocytes].

The frequency (f) of spontaneous contractions (SC) were registered on single enzymatically isolated cardiomyocytes of adult rats using current-carrying electrode through which current (50-200 nA) was passed. Cell motion on the electrode during SC caused current oscillations, measured by an amplifier. The actions of Na+, K+, Ca2+, caffeine, epinephrine and isoptin on fSC have been studied. The data obtained suggest that spontaneous contractions of isolated cardiomyocytes are related to increased intracellular Ca2+ concentration due to Na-Ca exchange. Cyclic contractions can possibly be accounted for by the work of sarcoplasmic reticulum.

Animals↗
PubMed1982

Sodium current in single internally perfused myocardial cells. Effects of ethmozine and lidocaine.

Voltage-clamp experiments were carried out, and sodium current (INa) was recorded on single rat cardiac cells perfused internally with Ca2+-free 140 mM Tris aspartate, 2 mM EGTA buffer, pH 7.3 at 20 degrees C. A voltage control microelectrode was impaled in the cell. Ethmozine (E), 0.08 mg/ml, and lidocaine (L), 0.08 mg/ml, were tested both inside and outside the cells. Although practically ineffective when administered inside the cell, E markedly affected INa when used externally. After 5 min of E treatment, the maximal INa was diminished to 43 +/- 6% (N = 6) of control value without any significant changes in the reactivation time constant tau re. Extra- and intracellular effects of L on INa were nearly equal. Internal L reduced the maximal INa to 31 +/- 5% (N = 7) of its initial value in 5 min; longer periods (8-10 min) were needed to obtain a similar effect with externally added L. Diminution of INa was accompanied by a delay in recovery; after 8 min of external L action, tau re increased from 17.5 +/- 1.7 msec (N = 4) to 142.5 +/- 19.9 msec (N = 4). It is supposed that ethmozine and lidocaine act at different sites on the cellular membrane.

Animals↗
PubMed1982

Characterization of the fast sodium current in isolated rat myocardial cells: simulation of the clamped membrane potential.

1. The fast sodium inward current of freshly isolated single rat myocardial cells was studied by means of the internal perfusion-voltage clamp method. 2. The voltage dependence of this current did not differ from the current-voltage characteristics of the fast sodium inward current described for other excitable cells and tissues. 3. The time constant of inactivation of the Na+ current of the isolated myocardial cells ranged between 5.2 msec at -58 mV and 0.5 msec at +18 mV. The activation time constant ranged from 0.3 msec at -55 mV to 70 microseconds at +10 mV. 4. The reactivation time constant of the maximum sodium current at a holding potential of -100 mV was found to be 21 +/- 5 msec. 5. A mathematical model was developed for the simulation and analysis of the influence of the series and shunt resistances on the time response of the membrane potential. The results of the modelling make it clear that control of the series and shunt resistances in any given experiment is a conditio sine qua non for a valid analysis of the kinetic parameters of the sodium inward current. 6. Sodium currents with delayed activation kinetics must be regarded as an indication of insufficient control of the membrane potential.

Animals↗
PubMed1982

[Effect of diethylamine analog of ethmozine on parameters of sodium current in isolated rat cardiomyocytes].

Voltage clamp experiments were made on ezymically isolated and internally perfused rat cardiac cells. The effect of a diethylamine analog of ethmozine (DAAE) on sodium current (INa) was tested when the drug was applied inside or outside the cell. It was found that the effect of DAAE (8 X 10(-6) g/ml) on INa was asymmetrical: after DAAE addition outside the cell, the amplitude of INa was effectively suppressed. Thus, 5 minutes after DAAE action the maximal value of INa in a voltage-current relationship was 20% of the control value without significant changes in the kinetics of INa. When the DAAE was added inside the cell preferentially, the inactivation time constant was increased without significant changes in the amplitude of the maximal INa. The same results were obtained with pronase (1 mg/ml) added inside the cell. It was supposed that as compared to ethmozine, the DAAE possesses a supplementary binding site on the cardiac cell membrane possibly linked to the structures responsible for inactivation processes.

Animals↗
PubMed1980

Voltage clamp method on single cardiac cells from adult rat heart.

Voltage clamp experiments on isolated cardiac cells from adult rat hearts were carried out using an intracellular dialysis method. The fast inward current was recorded. Tetrodotoxin (TTX) at a concentration of 2.5 x 10(-7) g/ml blocked this current to 30% of its initial value. Inward maximal fast current density was calculated to be 0.14--0.7 mA/cm2.

Animals↗
PubMed1980

[Changes in the sodium current under the action of etmozin and lidocaine inside and outside the membrane of single rat myocardial cells].

The voltage clamp experiments were carried out on single internally perfused rat myocardial cells. The effect of ethmozine (8 x 10(-5) g/ml) and lidocain (8 x 10(-6) g/ml) on the fast maximum inward sodium current (INa) was studied. The drugs were tested inside and outside the cell. INa was inhibited insignificantly when ethmozine was added inside the cell. After 5 min of ethmozine action outside the cell INa dropped on the average to 43 +/- 6% of its initial value. Under these conditions the reactivation constrant of INa did not change significantly. Lidocain depressed INa both when added outside and inside the cell. However, when lidocain was added outside the cell a longer period was needed to depress INa. Comparison of lidocain and ethmozine action outside and inside the myocardial cell has shown that the sites of action of these antiarrhythmic drugs on the cellular membrane are different.

Animals↗