On the role of sodium ions in the regulation of the inward-rectifying potassium conductance in cat ventricular myocytes

• Published in: The Journal of general physiology 1989-08, Vol.94 (2), p.329-348
• Main Authors: HARVEY, R. D, TEN EICK, R. E
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Calcium - metabolism; Cats; Electric Conductivity; Fundamental and applied biological sciences. Psychology; Heart; Heart Ventricles - metabolism; Hydrogen-Ion Concentration; In Vitro Techniques; Intracellular Fluid - metabolism; Ion Exchange; Membrane Potentials; Myocardium - metabolism; potassium; Potassium - metabolism; Potassium Channels - metabolism; sodium; Sodium - metabolism; Vertebrates: cardiovascular system
• ISSN: 0022-1295; 1540-7748
• DOI: 10.1085/jgp.94.2.329

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.