Effects on transmembrane action potential, slow inward current and force of contraction in ventricular cardiac muscle of BRL 31660, a new antiarrhythmic drug with class I and class IV activity

1985 ◽  
Vol 329 (1) ◽  
pp. 86-93 ◽  
Author(s):  
Reinhard Br�ckner ◽  
Wilhelm Schmitz ◽  
Hasso Scholz
Keyword(s):  
Action Potential ◽  
Cardiac Muscle ◽  
Antiarrhythmic Drug ◽  
Class I ◽  
Slow Inward Current ◽  
Force Of Contraction ◽  
Inward Current ◽  
Transmembrane Action Potential ◽  
Class Iv

Effects of ischemic conditions and reperfusion on depolarization-induced automaticity

1988 ◽  
Vol 255 (5) ◽  
pp. H992-H999 ◽  
Author(s):  
R. Mohabir ◽  
G. R. Ferrier
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Action Potentials ◽  
Cycle Length ◽  
Slow Inward Current ◽  
Potential Range ◽  
Ischemia And Reperfusion ◽  
Slow Response ◽  
Inward Current ◽  
High Membrane Potential

The inducibility of slow-response automaticity was assessed during ischemic conditions and reperfusion by application of extracellular current. Isolated canine Purkinje fibers were depolarized to membrane potentials less than -65 mV to elicit depolarization-induced automaticity (DIA). Ischemic conditions increased the cycle length of DIA and, in some tissues, prevented sustained DIA or completely abolished DIA. The magnitude of depolarization required to elicit DIA also increased. Inhibition of DIA occurred at a time when action potential plateaus were abbreviated. The effect of reperfusion on DIA was biphasic. Initial reappearance of DIA was followed by inhibition and reduction of the membrane potential range over which DIA could be elicited. Plateaus of action potentials initiated at high membrane potential were abbreviated at this time. DIA returned again as reperfusion effects dissipated. Phasic changes in the inducibility of DIA may represent changes in availability of the slow inward current and may regulate the timing and types of arrhythmic activity occurring with ischemia and reperfusion.

The toxic effects of ouabain: A voltage-clamp study

1982 ◽  
Vol 60 (9) ◽  
pp. 1153-1159 ◽  
Author(s):  
Y. Deslauriers ◽  
E. Ruiz-Ceretti ◽  
O. F. Schanne ◽  
M. D. Payet
Keyword(s):  
Action Potential ◽  
Voltage Clamp ◽  
Sodium Current ◽  
Negative Inotropic Effect ◽  
Slow Inward Current ◽  
Inward Current ◽  
Toxic Concentration ◽  
Voltage Curve ◽  
Current Voltage Curve ◽  
High Concentrations

The electrophysiologic effects of a toxic concentration of ouabain (10−5 M) were studied in frog atrial trabeculae. The toxic concentration was determined by the appearance of a negative inotropic effect and an increase in basal tension. Current- and voltage-clamp measurements were performed. Ouabain did not alter the passive electrical properties of the preparation. Under current-clamp conditions the membrane depolarized and the action potential amplitude as well as its maximum rate of rise decreased. The current–voltage curve for the fast inward current was shifted toward more positive potentials and the maximum sodium current decreased. The maximum sodium conductance was also reduced. The process of reactivation of the fast inward current was accelerated. The slow inward current and the maximum slow conductance also decreased under ouabain. These effects could explain the negative inotropic action of high concentrations of glycosides, as well as the action potential changes observed by several investigators. They also help to understand the arrhythmogenic effects of high concentrations of digitalis.

Slow inward current may produce many results attributed to IX1 in cardiac Purkinje fibers

1985 ◽  
Vol 249 (1) ◽  
pp. H122-H132
Author(s):  
J. M. Jaeger ◽  
W. R. Gibbons
Keyword(s):  
Action Potential ◽  
Outward Current ◽  
Purkinje Fiber ◽  
Slow Inward Current ◽  
Channel Blockers ◽  
Inward Current ◽  
Purkinje Fibers ◽  
Cardiac Purkinje Fibers ◽  
Current Voltage ◽  
Current Voltage Relation

We have tried to answer two fundamental questions concerning the outward current IX1 of cardiac Purkinje fibers. 1) Is it possible that current changes identified as arising from IX1 in voltage-clamp experiments are actually manifestations of changes in the slow inward current (Isi); and 2) is IX1 in fact required to produce the electrical phenomena attributed to it? Isi behavior and the role of IX1 were explored using computer simulation. The Isi model produced current changes during depolarizations and hyperpolarizations from depolarized resting potentials like those attributed to IX1. It also produced a component of "tail currents" that behaved like IX1. If these current changes were analyzed, assuming that an outward current is responsible, the resulting kinetics and current voltage relation would be very similar to the kinetics and current voltage relation reported for IX1. Using the McAllister, Noble, and Tsien formulation of the Purkinje fiber action potential, we found that IX1 is not essential for repolarization of the reconstructed action potential nor is it needed to reproduce interval duration effects and the effects of applied current in that model. Data suggesting that calcium channel blockers reduce IX1 and that catecholamines increase IX1 may be explained as arising from changes in Isi. Thus many manifestations of IX1 can be explained as arising from unanticipated behavior of Isi, and IX1 does not necessarily play a key role in generating Purkinje fiber electrical activity.

Participation of slow inward current in the Purkinje fiber action potential overshoot

1979 ◽  
Vol 237 (2) ◽  
pp. H204-H212
Author(s):  
L. Mary-Rabine ◽  
B. F. Hoffman ◽  
M. R. Rosen
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Purkinje Fiber ◽  
Slow Inward Current ◽  
Inward Current ◽  
Slow Channel ◽  
Phase 0 ◽  
Relationship Of ◽  
The Relationship ◽  
Diastolic Potential

We used microelectrode techniques to study the relationship of canine Purkinje fiber membrane potential and the action potential (AP) overshoot. At the maximum diastolic potential, -93.0 +/- 0.5 (SE) mV, AP overshoot was +37.7 +/- 0.4 mV. There was a range of membrane potentials (MP) less negative than the maximum diastolic potential from which action potentials were elicited with an overshoot greater than the control. Starting at an MP of less than -78.7 +/- 0.4 mV, AP overshoot was less than control. A maximum overshoot of +40.2 +/- 0.4 mV occurred at an MP of -85.4 +/- 0.4 mV. The relationship of the maximum upstroke velocity (Vmax) of phase 0 depolarization to MP was sigmoidal. Peak Vmax, 497 +/- 13 V/s, occurred at MP greater than or equal to -89.3 +/- 0.5 mV. The increase in overshoot was enhanced as perfusate [Ca2+] increased and decreased as [Ca2+] decreased. Slow-channel blocking agents and tetrodotoxin (TTX) depressed the peak of the curve relating overshoot to MP. TTX also decreased Vmax. The effect of TTX on overshoot but not on Vmax was reversed with Ca2+, 8.1 mM. The increase in overshoot for action potentials initiated during the terminal part of phase 3 was due to a slow, delayed component of the upstroke and appears to result from the slow inward current.

Blockade of myocardial slow inward current at low pH

1977 ◽  
Vol 233 (3) ◽  
pp. C99-C103 ◽  
Author(s):  
S. Vogel ◽  
N. Sperelakis
Keyword(s):  
Electrical Stimulation ◽  
Action Potential ◽  
Low Ph ◽  
Slow Inward Current ◽  
Embryonic Chick ◽  
Slow Response ◽  
Na Current ◽  
Inward Current ◽  
Acid Ph ◽  
Subsequent Exposure

The effect of low pH on the slow cationic inward current was studied in isolated perfused embryonic chick ventricles (16-21 days old). In order to study the slow current, the fast Na+ current was inactivated by partial depolarization to about -40 mV by elevation of K+ (25 mM). Subsequent exposure of the tissue to catecholamines or methylxanthines allowed slowly rising overshooting electrical responses (the "slow response") with with accompanying contractions to be elicited by electrical stimulation. These slow responses are insensitive to tetrodotoxin and are Na+- and Ca2+-dependent. It was found that the isoproterenol- and caffeine-induced slow responses were abolished at about pH 6.1; 50% inhibition occurred at about pH 6.5. The rate of rise of the normal action potential, which is dependent on a fast Na+ current, was only slightly affected at these same pH levels; however, electromechanical uncoupling occurred, as expected from inhibition of the slow current. Therefore, the slow current was blocked at an acid pH that did not block the fast Na+ current.

Existence and role of a slow inward current during the frog atrial action potential

1969 ◽  
Vol 308 (2) ◽  
pp. 91-110 ◽  
Author(s):  
O. Rougier ◽  
G. Vassort ◽  
Y. M. Gargouil ◽  
E. Coraboeuf
Keyword(s):  
Action Potential ◽  
Slow Inward Current ◽  
Inward Current

Opposite change with ischaemia in the antifibrillatory effects of class I and class IV antiarrhythmic drugs resulting from the alteration in ion transmembrane exchanges related to depolarization

2000 ◽  
Vol 78 (3) ◽  
pp. 208-216 ◽  
Author(s):  
Jean-François Aupetit ◽  
Bernard Bui-Xuan ◽  
Idriss Kioueh ◽  
Joseph Loufoua ◽  
Dominique Frassati ◽  
...  
Keyword(s):  
Action Potential ◽  
Calcium Channel ◽  
Sodium Channel ◽  
Sodium Channels ◽  
Antiarrhythmic Drugs ◽  
Channel Blocker ◽  
Class I ◽  
Monophasic Action Potential ◽  
Channel Blockers ◽  
Class Iv

It is known that class I antiarrhythmic drugs lose their antifibrillatory activity with severe ischaemia, whereas class IV antiarrhythmic drugs acquire such activity. Tachycardia, which is also a depolarizing factor, has recently been shown to give rise to an alteration of ion transmembrane exchanges which is particularly marked in the case of calcium. This leads one to wonder if the change in antifibrillatory activity of antiarrhythmic drugs caused by ischaemia depends on the same process. The change in antifibrillatory activity was studied in normal conditions ranging to those of severe ischaemia with a class I antiarrhythmic drug, flecainide (1.00 mg·kg-1 plus 0.04 mg·kg-1·min-1), a sodium channel blocker, and a class IV antiarrhythmic drug, verapamil (50 µg·kg-1 plus 2 µg·kg-1·min-1), a calcium channel blocker. The experiments were performed in anaesthetized, open-chest pigs. The resulting blockade of each of these channels was assessed at the end of ischaemic periods of increasing duration (30, 60, 120, 180, 300, and 420 s) by determining the ventricular fibrillation threshold (VFT). VFT was determined by means of trains of diastolic stimuli of 100 ms duration delivered by a subepicardial electrode introduced into the myocardium (heart rate 180 beats per min). Ischaemia was induced by completely occluding the left anterior descending coronary artery. The monophasic action potential was recorded concurrently for the measurement of ventricular conduction time (VCT). The monophasic action potential duration (MAPD) varied with membrane polarization of the fibres. The blockade of sodium channels by flecainide, which normally raises VFT (7.0 ± 0.4 to 13.8 ± 0.8 mA, p < 0.001) and lengthens VCT (28 ± 3 to 44 ± 5 ms, p < 0.001), lost its effects in the course of ischaemia. This resulted in decreased counteraction of the ischaemia-induced fall of VFT and decreased aggravation of the ischaemia-induced lengthening of VCT. The blockade of calcium channels, which normally does not alter VFT (between 7.2 ± 0.6 and 8.4 ± 0.7 mA, n.s.) or VCT (between 30 ± 2 and 34 ± 3 ms, n.s.), slowed the ischaemia-induced fall of VFT. VFT required more time to reach 0 mA, thus delaying the onset of fibrillation. Membrane depolarization itself was opposed as the shortening of MAPD and the lengthening of VCT were also delayed. Consequently there is a progressive decrease in the role played by sodium channels during ischaemia in the rhythmic systolic depolarization of the ventricular fibres. This reduces or suppresses the ability of sodium channel blockers to act on excitability or conduction, and increases the role of calcium channel blockers in attenuating ischaemia-induced disorders.Key words: pigs, ion transmembrane exchanges, myocardial ischaemia, sodium channel, calcium channel.

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