Effect of H+ on ATP-regulated K+ channels in feline ventricular myocytes.
Using patch-clamp techniques, we examined the effects of pH on properties of ATP-regulated K+ channels in single myocytes isolated from cat left ventricles. ATP-K+ channels of inside-out patches were bilaterally exposed to 140 mM K+ solutions (22 degrees C). In the absence of ATP and Mg2+, the channels had a linear current-voltage relationship during hyperpolarizing pulses (20-100 mV negative to the reversal potential) at both intracellular pH (pHi) 7.4 and 6.5, but the slope conductance was 66 +/- 2 pS at pHi 7.4 and 46 +/- 2 pS at pHi 6.5. Lowering pHi from 7.4 to 6.5 increased the mean open time (from 15.9 +/- 4.6 to 35.9 +/- 7.9 ms, P less than 0.01) but decreased the open-state probability measured at 50 mV positive to the reversal potential (from 0.35 +/- 0.04 to 0.16 +/- 0.04, P less than 0.01). However, in the presence of both 0.2 mM ATP and 1 mM MgCl2, lowering pHi from 7.4 to 6.5 increased the mean open time (from 5.0 +/- 2.6 to 17.9 +/- 5.9 ms, P less than 0.01) and the open-state probability (from 0.025 +/- 0.010 to 0.098 +/- 0.024, P less than 0.01). These data indicate that increases in intracellular H+ concentration modulate cardiac ATP-K+ channel properties. Ischemia-associated decreases in pHi may enhance the opening of cardiac ATP-regulated K+ channels and resultant action potential shortening.
Cuevas
J
J
Department of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Florida 33101.
Bassett
A L
AL
Cameron
J S
JS
Furukawa
T
T
Myerburg
R J
RJ
Kimura
S
S
D000255:Adenosine Triphosphate / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D002415:Cats; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004553:Electric Conductivity / Q000187:drug effects; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles; D006863:Hydrogen-Ion Concentration; D015636:Magnesium Chloride / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011336:Probability
D015221:Potassium Channels; D015636:Magnesium Chloride; D000255:Adenosine Triphosphate