Repolarization of the mammalian heart action potential is modulated by changes in osmotic strength

Abstract

This editorial refers to ‘Osmotic modulation of slowly activating I Ks in guinea-pig ventricular myocytes’ by S. Missan et al ., pp. 429–436, this issue. Repolarization of the mammalian heart action potential is a very important physiological variable. It sets action-potential duration and thus strongly modulates contractility and refractoriness in both the atria and the ventricles. Repolarization is initiated and controlled by the time- and voltage-dependent onset of a variety of different outward potassium (K+) currents, some of which are highly non-linear.1 One of these currents, the so-called slow outward delayed rectifier, or I Ks, is expressed in the human ventricle. Its activation adds to the safety factor for repolarization (the so-called repolarization reserve) through its intrinsic time and voltage dependence. This is prominent following augmentation of I Ks by sympathetic nerve stimulation.2 A paper in this issue from the McDonald laboratory3 confirms and extends what is known about the modulation of I Ks in response to changes in osmotic strength of the external medium. A significant change in osmotic strength (±20–30%) may take place in the setting of ischaemia–reperfusion of the heart. This paper demonstrates relatively rapid (3–5 min to steady state) changes in I Ks in single ventricular myocytes obtained from the hearts of adult guinea pigs in response to alterations in osmotic strength: reductions result in reversible increases in I Ks and vice versa. These changes appear to be quite selective as judged by the reported lack of effect on a selected K+ current denoted HERG. The context for these findings and some aspects of their interpretation is aided …