Effects of quinine and quinidine on the transient outward and on the L-type Ca(2+) current in rat ventricular cardiomyocytes.
The effects of the enantiomers quinine and quinidine on the transient outward current (I(to)) and on the L-type Ca(2+) 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 micromol/l, respectively, and those on I(Ca) at 14 and 10 micromol/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).
Michel
Delia
D
Pharmakologisches Institut, Johannes Gutenberg-Universität, Mainz, Deutschland.
Wegener
Jörg W
JW
Nawrath
Hermann
H
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000737:chemistry / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D020746:Calcium Channels, L-Type / Q000187:drug effects; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D011802:Quinidine / Q000737:chemistry / Q000494:pharmacology*; D011803:Quinine / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
D000889:Anti-Arrhythmia Agents; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D011803:Quinine; D011802:Quinidine