Does small-conductance calcium-activated potassium channel contribute to cardiac repolarization?
Small-conductance calcium-activated potassium channels (SK channels) have a significant role in neurons. Since they directly integrate calcium handling with repolarization, in heart their role would be particularly important. However, their contribution to cardiac repolarization is still unclear. A previous study reported a significant lengthening effect of apamin, a selective SK channel inhibitor, on the action potential duration in atrial and ventricular mouse cardiomyocytes and human atrial cells. They concluded that these channels provide an important functional link between intracellular calcium handling and action potential kinetics. These findings seriously contradict our studies on cardiac "repolarization reserve", where we demonstrated that inhibition of a potassium current is not likely to cause excessive APD lengthening, since its decrease is mostly compensated by a secondary increase in other, unblocked potassium currents. To clarify this contradiction, we reinvestigated the role of the SK current in cardiac repolarization, using conventional microelectrode and voltage-clamp techniques in rat and dog atrial and ventricular multicellular preparations, and in isolated cardiomyocytes. SK2 channel expression was confirmed with immunoblot technique and confocal microscopy. We found, that while SK2 channels are expressed in the myocardium, a full blockade of these channels by 100 nM apamin--in contrast to the previous report--did not cause measurable electrophysiological changes in mammalian myocardium, even when the repolarization reserve was blunted. These results clearly demonstrate that in rat, dog and human ventricular cells under normal physiological conditions--though present--SK2 channels are not active and do not contribute to action potential repolarization.
Nagy
Norbert
N
Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary.
Szuts
Viktória
V
Horváth
Zoltán
Z
Seprényi
György
G
Farkas
Attila S
AS
Acsai
Károly
K
Prorok
János
J
Bitay
Miklós
M
Kun
Attila
A
Pataricza
János
J
Papp
Julius Gy
JG
Nánási
Péter P
PP
Varró
András
A
Tóth
András
A
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D015153:Blotting, Western; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism / Q000502:physiology*
D051640:Small-Conductance Calcium-Activated Potassium Channels; D001030:Apamin