Propafenone blocks ATP-sensitive K+ channels in rabbit atrial and ventricular cardiomyocytes.
Propafenone, a class I antiarrhythmic agent, inhibits several membrane currents (I(Na), I(Ca), I(K), Ito), however, its effects on ATP-sensitive potassium current (I(K)ATP) of cardiac cells have not been tested. We evaluated the blocking effects of 0.1 to 100 microM propafenone applications at 35 degrees C on the whole-cell I(K)ATP as triggered by dinitrophenol (75 microM) in adult rabbit dissociated atrial and ventricular cardiomyocytes in comparison. The block of I(K)ATP by propafenone was dose-dependent, fully reversible and voltage-independent. The dose-response relation, as evaluated at 0 mV for atrial myocytes (ED50 = 1.26+/-0.17 microM, Hill number = 1.25+/-0.22) was significantly shifted to the left vs. that in ventricular myocytes (ED50 = 4.94+/-0.59 microM, Hill number = 1.22+/-0.14). It is concluded that propafenone blocks cardiac I(K)ATP at a single site with 4 times higher affinity for the drug in atrial myocytes. This block of cardiac I(K)ATP might play a role in the beneficial and adverse effects of the drug.
INSERM U 121, Bron, France. georges.christe@ujf-grenoble.fr
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G
Christé
H
H
Tebbakh
M
M
Simurdová
R
R
Forrat
J
J
Simurda
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D016275:Atrial Function; D004140:Dinitrophenols / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D006325:Heart Atria / Q000166:cytology / Q000187:drug effects*; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D011405:Propafenone / Q000494:pharmacology*; D011817:Rabbits; D014475:Uncoupling Agents / Q000494:pharmacology; D016276:Ventricular Function
D000889:Anti-Arrhythmia Agents; D004140:Dinitrophenols; D026902:Potassium Channel Blockers; D014475:Uncoupling Agents; D011405:Propafenone; D000255:Adenosine Triphosphate