On the role of sodium ions in the regulation of the inward-rectifying potassium conductance in cat ventricular myocytes.
The conductance of the inward-rectifying K+ current (IK1) in isolated cat ventricular myocytes is decreased by reducing the extracellular Na+ concentration. Using a whole-cell patch-clamp technique, possible mechanisms underlying this Na+ dependence were investigated. These included (a) block of inward K+ current by the Na+ substitute, (b) changes in membrane surface charge associated with removal of extracellular Na+, (c) increases of intracellular Ca2+ due to suppression of Na-Ca exchange, (d) reduction of a Na+-dependent K+ conductance due to a subsequent decrease of intracellular Na+, (e) reduction of IK1 conductance (gK1) associated with reduction of intracellular pH due to suppression of Na-proton exchange. The findings support the hypothesis that the effect of removing Na+ is mediated through a decrease in intracellular pH. These include observations that: (a) reducing internal pH by reducing external pH caused a decrease in gK1, and the conductance changes caused by reducing extracellular pH and removing extracellular Na+ were not additive: (b) the effect of reducing pHo was attenuated by dialyzing with a low pH internal solution; (c) gK1 was reduced by exposure to the Na-proton exchange inhibitor dimethylamiloride, and this effect was absent in the absence of Na+. These findings imply that physiological or pathological processes such as ischemia and metabolic or respiratory acidosis which can produce intracellular acidosis should be expected to affect K+ permeation through the IK1 channel.
Harvey
R D
RD
Department of Pharmacology, Northwestern University, Chicago, Illinois 60611.
Ten Eick
R E
RE
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002415:Cats; D004553:Electric Conductivity; D006352:Heart Ventricles / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D007474:Ion Exchange; D008564:Membrane Potentials; D009206:Myocardium / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*
D015221:Potassium Channels; D012964:Sodium; D011188:Potassium; D002118:Calcium