Osmotic modulation of slowly activating I _Ks in guinea-pig ventricular myocytes

Aims The aims of the study were to determine the effects of anisosmotic bathing solution on selected properties of / _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 IKs, and hyperosmotic solution decreased it. Anisosmotic-induced changes in IKs amplitude were complete in 25 min, well-maintained, reversible, and not accompanied by significant changes in IKs 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 IKs 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) IKs 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 doseresponse relation that predicts relatively strong responses of I _Ks to small perturbations in external osmolarity.