Verapamil diminishes action potential changes during metabolic inhibition by blocking ATP-regulated potassium currents.
Verapamil has beneficial effects on ischemic myocardium, including reduction in electrophysiological derangements, prevention of intracellular K+ loss, and preservation of high-energy phosphates, but the mechanisms underlying these actions are not clear. Recent studies have demonstrated a role of ATP-regulated K+ (KATP) current in action potential shortening and K+ loss during ischemia and metabolic inhibition. Therefore, we studied the effects of verapamil on KATP current in feline ventricular myocytes to test the hypothesis that the drug prevents ischemic electrophysiological disturbances by affecting the KATP channel. Membrane potentials and currents were recorded using standard patch-clamp techniques. During 15-minute superfusion with 1 mM CN-, action potential duration measured at 90% repolarization was reduced from 259 +/- 12 to 98 +/- 15 msec (62% reduction) in the absence of verapamil and from 266 +/- 11 to 183 +/- 16 msec (31% reduction) in the presence of 2 microM verapamil (p less than 0.01). In inside-out membrane patches, the KATP current, activated in the absence of ATP, was significantly suppressed by intracellular application of 2 microM verapamil, but the single-channel conductance was not changed. Verapamil did not change the mean open and closed times of the channel within bursts (e.g., the mean open time was 1.92 +/- 0.18 and 1.82 +/- 0.21 msec in the absence and presence of 2 microM verapamil, respectively), but it shortened the mean lifetime of bursts from 41.1 +/- 3.5 to 24.9 +/- 2.8 msec (p less than 0.01) and prolonged the closed time between bursts from 39.4 +/- 4.6 to 78.5 +/- 5.1 msec (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Kimura
S
S
Department of Medicine, University of Miami School of Medicine, FL 33101.
Bassett
A L
AL
Xi
H
H
Myerburg
R J
RJ
D000200:Action Potentials / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D002415:Cats; D003486:Cyanides / Q000494:pharmacology; D004594:Electrophysiology; D005260:Female; D007700:Kinetics; D008297:Male; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D014700:Verapamil / Q000494:pharmacology*
D003486:Cyanides; D015221:Potassium Channels; D000255:Adenosine Triphosphate; D014700:Verapamil