Osmotic modulation of slowly activating IKs in guinea-pig ventricular myocytes

Aims The aims of the study were to determine the effects of anisosmotic bathing solution on selected properties of I-Ks, the slowly activating delayed-rectifier K+ current important for repolarization of the action potential in cardiac cells. Methods and results Guinea-pig ventricular myocytes were voltage-clamped using either the ruptured-patch or perforated-patch technique, and the amplitude, time course, and voltage dependence of I-Ks were determined before [isosmotic (1T)] and during superfusion of hyposmotic (< 1T) or hyperosmotic (> 1T) bathing solution. Hyposmotic solution increased the amplitude of I-Ks, and hyperosmotic solution decreased it. Anisosmotic-induced changes in I-Ks amplitude were complete in 2-5 min, well-maintained, reversible, and not accompanied by significant changes in I-Ks time course and voltage dependence. There was little difference in the results obtained with the ruptured-patch technique and those obtained with the perforated-patch technique. The amplitude of I-Ks was sensitive to small (+/- 10%) changes in osmolarity, maximally increased by hyposmotic solution with T < 0.7, and strongly decreased by hyperosmotic solution with T > 1.5. Experimental data on a plot of relative (1T = 1.0) I-Ks amplitude vs. the reciprocal of relative osmolarity are well-described by a Hill equation that has a lower asymptote of 0.0, an upper asymptote of 2.0, and a slope factor of 1.87 +/- 0.07. Conclusion Modulation of I-Ks amplitude by anisosmotic solution is independent of patch configuration, unaccompanied by changes in current gating, and well-described by a Hill dose-response relation that predicts relatively strong responses of I-Ks to small perturbations in external osmolarity.