Early increase in K+ conductance during metabolic inhibition by cyanide in guinea pig ventricular myocytes.
The underlying mechanism of the early increase in K+ conductance during metabolic inhibition was examined by the whole-cell patch clamp technique. To inhibit oxidative phosphorylation, cyanide (0.1-1.0 mM) was superfused to enzymatically isolated guinea pig ventricular myocytes. The increase in the outward K+ current during the metabolic inhibition consisted of at least two components; one was a gradual and small increase which appeared within 5 min, and the other was a subsequent sudden and large increase occurring 17.8 min on average after cyanide application at a concentration of 0.1 mM. The earlier component of the cyanide-sensitive current was examined by the square pulse method. The current had a reversal potential of -76.0 mV and an inward-rectifying property. When cyanide (0.1 mM) was applied for 10-12 min, the chord conductance of the inward rectifier K+ current (IK1) was significantly increased and its voltage relation was shifted to hyperpolarizing direction (-2.3 mV). The cyanide could not induce an outward current in K(+)-free ionic condition or in the presence of extracellular Ba2+ (2 mM), a blocker of the IK1. However, the outward current even appeared in the presence of 5 mM ATP in the perfused solution in pipette, while it attenuated when intracellular pH was buffered with 50 mM HEPES in the pipette solution. These observations suggest that the early increase in K+ conductance during the metabolic inhibition is due to the augmented IK1 conductance and not due to the induction of ATP-sensitive K+ current. The increase in the K+ conductance may be caused by the intracellular pH change, probably through intracellular metabolic acidosis by the inhibited oxidative phosphorylation.
Muramatsu
H
H
First Department of Internal Medicine, Nippon Medical School.
Sato
R
R
Okumura
H
H
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003486:Cyanides / Q000494:pharmacology*; D003864:Depression, Chemical; D006168:Guinea Pigs; D006352:Heart Ventricles; D006863:Hydrogen-Ion Concentration; D008564:Membrane Potentials; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D011188:Potassium / Q000378:metabolism*
D003486:Cyanides; D000255:Adenosine Triphosphate; D011188:Potassium