The Effect of Quinidine on Membrane Electrical Activity in Frog Auricular Fibres Studied by Current and Voltage Clamp

Ducouret, Pierre

doi:10.1111/j.1476-5381.1976.tb07465.x

Cited by 57 publications

(24 citation statements)

References 27 publications

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“…Voltage-clamp data showed that both slow inward and outward currents were reduced by quinidine (Nawrath, 1981). Similar findings were obtained in frog atrial fibres (Ducouret, 1976).…”

Section: Comparison With Verapamilsupporting

confidence: 76%

“…This has already been pointed out by other investigators studying these agents (Arnsdorf& Bigger, 1975;1976;Carmeliet & Saikawa, 1982;Colatsky, 1982). It should be emphasized, however, that the preparation used here showed one to two orders of magnitude less sensitivity to the antiarrhythmic agents than the mammalian preparations frequently used in other investigations.…”

Section: Comparison With Verapamilmentioning

confidence: 45%

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Effects of lidocaine, procaine, procainamide and quinidine on electrophysiological properties of cultured embryonic chick hearts

Neto

Sperelakis

1985

British J Pharmacology

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The effects of lidocaine, procaine, procainamide and quinidine were studied on organ‐cultured embryonic chick (2–3 day‐old) ventricular cells. Lidocaine (10−5 − 10−4 M), in a dose‐dependent manner, reduced the rate of pacemaker discharge, the action potential amplitude (APA), the maximum rate of rise (Vmax) of the upstroke of the action potential and the action potential duration at 50% repolarization (APD50). These changes occurred without alterations in the maximum diastolic potential (MDP). Extracellular electrical field stimulation could still evoke action potentials in cells arrested by 10−4 M lidocaine, but 10−3 M lidocaine completely abolished electrical activity. Procaine, procainamide and quinidine, at 5 × 10−5 M to 10−3 M, depolarized the cells to around − 30 mV and reduced APA and Vmax. Procaine and procainamide increased APD50, but quinidine shortened it. All the effects described disappeared completely in about 40 min of superfusion with drug‐free Tyrode solution. Isoprenaline (5 × 10−7 M) and adrenaline (10−6 M) restored spontaneous firing of preparations arrested by any of the antiarrhythmic agents and repolarized ventricular cells depolarized by procaine, procainamide or quinidine. Propranolol (5 × 10−7 M) did not affect the depolarization produced by procaine (5 × 10−4 M), but antagonized its reversal by isoprenaline. In contrast, isoprenaline (10−6 M) did not produce recovery of automaticity of preparations arrested by verapamil (10−5 M). Histamine (10−5 M) or strontium (10 mM) were not able to restore rhythmic activity in cells arrested procaine. Application of long (10–15 s duration) hyperpolarizing currents did not reverse the blocking effect of procaine, procainamide and quinidine. The input resistance increased during the procaine‐induced depolarization. It is suggested that the four agents studied block the slow Na+ channels responsible for the upstroke of the action potential in young chick heart cells. A drug‐induced decrease in PK may occur in those cells arrested at low levels of membrane potential.

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“…Voltage-clamp data showed that both slow inward and outward currents were reduced by quinidine (Nawrath, 1981). Similar findings were obtained in frog atrial fibres (Ducouret, 1976).…”

Section: Comparison With Verapamilsupporting

confidence: 76%

Section: Comparison With Verapamilmentioning

confidence: 45%

Effects of lidocaine, procaine, procainamide and quinidine on electrophysiological properties of cultured embryonic chick hearts

Neto

Sperelakis

1985

British J Pharmacology

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“…[24][25][26][27] The effect of quinidine to prolong APD and produce EAD-induced triggered activity may be ascribed chiefly to the drug's action to inhibit the delayed rectifier because diminution of the other currents would be expected to abbreviate APD and prevent the emergence of EAD and triggered activity or exert little effect. Imaizumi and Giles28 recently reported quinidine's effect to inhibit the transient outward current in isolated rabbit myocytes.…”

Section: Ionic Mechanismsmentioning

confidence: 99%

Quinidine-induced action potential prolongation, early afterdepolarizations, and triggered activity in canine Purkinje fibers. Effects of stimulation rate, potassium, and magnesium.

et al. 1989

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Early afterdepolarization (EAD)-induced triggered activity is thought to contribute to the cardiac arrhythmogenic effects of several class I antiarrhythmic agents. The combination of quinidine therapy, bradycardia, and hypokalemia is known to predispose to torsade de pointes, which is a form of atypical polymorphous ventricular tachycardia commonly associated with long QT intervals. Recent clinical reports have shown suppression of quinidine-induced torsade de pointes with intravenous administration of magnesium sulfate. To provide further understanding of these relations, we used standard microelectrode techniques to examine the time course of quinidineinduced action potential prolongation, EAD, and triggered activity development and the dependence of these changes on [K+]0, [Mg2+]O, and stimulation frequency in isolated Purkinje fiber preparations exposed to low concentrations of the drug. At slow stimulation rates, the quinidineinduced increase of action potential duration was slow to develop and failed to reach a steady state after 3 hours of exposure to the drug. EAD and EAD-induced triggered activity generally became apparent 70-90 minutes after adding the drug. Quinidine produced triggered activity in 10 of 22 preparations superfused with Tyrode's solution containing normal [K+]0 (3.5-4.0 mM) and in six other preparations when [K%]0 was reduced. In the presence of normal [K]0, two types of EAD and triggered activity were distinguished. In four of 10 preparations, this activity arose from phase 2 of the action potential; in eight of 10, it was associated with phase 3; and in two experiments, both types were present in the same preparation. The incidence of both forms of triggered responses depended greatly on the rate of stimulation. Triggered activity arising from phase 3 was always manifest at rates considerably slower than those giving rise to phase 2 activity. Both forms of triggered activity were sensitive to changes in the extracellular concentration of potassium and magnesium. Lower-than-normal levels of these electrolytes facilitated the manifestation of triggered activity, whereas elevated levels suppressed or caused a shift in the frequency-dependence of the activity. In the clinic, the combination of bradycardia, hypokalemia, and quinidine is known to predispose to torsade de pointes, which is a form of atypical polymorphous ventricular tachycardia characterized in the electrocardiogram by "twisting" of the ventricular complexes around the isoelectric line. Torsade de pointes is commonly associated with QT

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“…For historical reasons, quinidine has been studied more thoroughly than probably any other anti-arrhythmic drug. Most investigators have found that quinidine prolongs APD (Vaughan Williams, 1958;West & Amory, 1960;Ducouret, 1976;Nawrath & Eckel, 1979;Nawrath, 1981;Nattel & Zeng, 1984). However, the magnitude of quinidine-induced prolongation of APD has been shown to depend upon experimental conditions.…”

Section: Discussionmentioning

confidence: 99%

A comparison of the effects of bethanidine, meobentine and quinidine on the electrical activity of rat hearts in vivo and in vitro

Northover

1985

British J Pharmacology

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Polytechnic, Leicester LEI 9BH 1 Glass microelectrodes were used to record transmembrane electrical activity from cells located just beneath the endocardial surface of segments of the right ventricular free wall of the rat heart during superfusion and electrical stimulation in vitro at 37°C. 2 The sulphates of bethanidine, meobentine or quinidine (4 to 20riM) applied in vitro caused a prolongation of action potential duration and a delayed and slowed return of electrical excitability following an action potential. 3 Intracardiac electrical stimulation of the urethane-anaesthetized rat heart in situ was used to measure ventricular refractory periods from the electrocardiogram. 4 Intravenous administration of bethanidine, meobentine or quinidine (10 to 20mg kg-')caused a prolongation ofventricular refractory periods. Quinidine had a briefer duration ofaction than either of the other two drugs tested. 5 Urethane-anaesthetized open-chested rats which were subjected to left coronary artery occlusion displayed ventricular tachyarrhythmias in their electrocardiogram. These arrhythmias occurred during the period of occlusion and even more prominently after release of the occlusion. Intravenous administration of bethanidine, meobentine or quinidine (I to 20 mg kg-') protected rats against these arrhythmias. The protective effect of quinidine was briefer than that of either of the other two drugs tested.

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The Effect of Quinidine on Membrane Electrical Activity in Frog Auricular Fibres Studied by Current and Voltage Clamp

Cited by 57 publications

References 27 publications

Effects of lidocaine, procaine, procainamide and quinidine on electrophysiological properties of cultured embryonic chick hearts

Effects of lidocaine, procaine, procainamide and quinidine on electrophysiological properties of cultured embryonic chick hearts

Quinidine-induced action potential prolongation, early afterdepolarizations, and triggered activity in canine Purkinje fibers. Effects of stimulation rate, potassium, and magnesium.

A comparison of the effects of bethanidine, meobentine and quinidine on the electrical activity of rat hearts in vivo and in vitro

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