Unanticipated lessening of the rise in extracellular potassium during ischemia by pinacidil.
BACKGROUND
The efflux of potassium (K) through the ATP-sensitive K channel is considered an important cause of the rise in extracellular K ([K+]e) during no-flow ischemia. We postulated that agents that enhance K conductance in this channel would enhance the rise in [K+]e.


RESULTS
We studied the effects of 10 and 25 mumol/L pinacidil, and ATP-sensitive K channel opener that provides metabolic protection to the ischemic myocardium, on the rise in [K+]e recorded by K-sensitive electrodes, the change in action potential duration (APD) recorded by microelectrodes, and the changes in activation during ischemia in in situ pig hearts and Tyrode-perfused rabbit interventricular septa. Pinacidil 25 mumol/L unexpectedly lessened the rise in [K+]e and the activation delay in both preparations. Pinacidil 10 mumol/L had no effect in the rabbit and only a slight effect in the pig. Both concentrations significantly exaggerated the APD shortening induced by ischemia. By varying stimulation frequency, we demonstrated that the rise in [K+]e during ischemia, both before and after pinacidil, correlated with the time that the action potential was at its plateau voltage.


CONCLUSIONS
Our results indicate that the rise in [K+]e during ischemia is due to multiple factors, including K conductance across membrane channels, K driving force as reflected by the time that the action potential is at its plateau voltage, and the metabolic effects of ischemia. The unanticipated lessening of the rise in [K+]e by pinacidil reflects the balance of its effects on these several parameters.
Kanda
A
A
Department of medicine, University of North Carolina at Chapel Hill, USA.
Watanabe
I
I
Williams
M L
ML
Engle
C L
CL
Li
S
S
Koch
G G
GG
Gettes
L S
LS
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D004353:Drug Evaluation, Preclinical; D005260:Female; D006146:Guanidines / Q000494:pharmacology* / Q000627:therapeutic use; D015640:Ion Channel Gating / Q000187:drug effects*; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000378:metabolism*; D015425:Myocardial Reperfusion; D020110:Pinacidil; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects*; D011817:Rabbits; D013552:Swine; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use
D006146:Guanidines; D015221:Potassium Channels; D014665:Vasodilator Agents; D020110:Pinacidil; D000255:Adenosine Triphosphate; D011188:Potassium