Effects of Quinine and Quinidine on the Transient Outward and on the L-Type Ca²⁺ Current in Rat Ventricular Cardiomyocytes

Abstract

The effects of the enantiomers quinine and quinidine on the transient outward current (I_to) and on the L-type Ca²⁺ current (I_Ca) were investigated in rat ventricular cardiomyocytes using the patch-clamp technique. At a stimulation frequency of 2 Hz, both quinine and quinidine depressed the magnitude of I_to and I_Ca; the half-maximal effects on I_to were achieved at 11 and 15 µmol/l, respectively, and those on I_Ca at 14 and 10 µmol/l, respectively. At 0.2 Hz, both drugs depressed the magnitude of I_to, but not that of I_Ca. A change in extracellular pH from 7.3 to 8.3 did not significantly influence the effects of the drugs (which are protonated to 98% at pH 7.3) on I_to or I_Ca. It is concluded that neither the different chemical structure nor the amount of protonation of quinine and quinidine controls their effects on I_to or I_Ca.

Pressor responses to platelet-activating factor and thromboxane are mediated by Rho-kinase

“…This is in line with observations in platelets showing that Ca 2ϩ influx in human platelets occurs independently of IP 3 (49). The present findings also help us to better understand the inhibitory effect on PAF-induced thromboxane synthesis of quinine (7), which among other things may block IP 3 receptors (18), Ca 2ϩ channels (27), and PLA 2 (19). Cytosolic PLA 2 is a calciumdependent enzyme that is critical for arachidonic acid and thus thromboxane formation (23).…”

QT PRODACT: Evaluation of the Potential of Compounds to Cause QT Interval Prolongation by Action Potential Assays Using Guinea-Pig Papillary Muscles

“…On the other hand, despite the fact that disopyramide (13), quinidine (14,17), and pimozide (16) inhibit I Ca , they prolonged APD , APD 60-90 , and APD . Therefore, it is likely that evaluation of the effects of compounds on APD 30-60 , APD 60-90 , and APD can predict the inhibitory effects of mixed ion-channel blockers on I Kr and / or hERG currents, although no difference in sensitivity, when evaluating the inhibitory effects of mixed ion-channel blockers on hERG, can be expected between APD 30-60 , APD 60-90 , and APD 30-90 measurement.…”

“…The 21 test compounds used in this study were divided into three groups: 1) I Kr and / or hERG current inhibitors reported to inhibit calcium currents: bepridil (11), cisapride (12), disopyramide (13), flecainide (14), haloperidol (15), pimozide (16), quinidine (14,17), terfenadine (18,19), and verapamil (20); 2) I Kr and / or hERG current inhibitors not reported to inhibit calcium currents (21): astemizole, ciprofloxacin, E-4031, MK-499, dl-propranolol, and thioridazine; and 3) other compounds with little or no effect on hERG currents (21): amoxicillin, aspirin, captopril, diphenhydramine, lidocaine, and nifedipine.…”

FUNCTIONAL IMPAIRMENT OF CARDIAC TRANSIENT OUTWARD K+ CURRENT AS A RESULT OF ABNORMALLY ALTERED CELLULAR ENVIRONMENT

“…To our knowledge, four classes of anti‐arrhythmic drugs inhibit I to to varying extents. The class I anti‐arrhythmic drugs quinidine, lignocaine and flecainide have been shown to block I to at clinical doses; 10,11 the class II anti‐arrhythmic drugs, β‐adrenoceptor antagonists, inhibit transient and delayed outward K + currents; 12 and the class III anti‐arrhythmic drug amiodarone can act on multiple targets at same time and affects many K + channels, including I to (IC 50 approximately 4.9 µmol/L), in addition to blocking Na + and Ca 2+ channels 13,14 . The effects of the class IV anti‐arrhythmic drug verapamil on I to are similar to those of quinidine.…”