Properties of sodium and potassium currents of cultured adult human atrial myocytes

Abstract

Cultured cell systems are valuable for the study of regulation of phenotypic expression, but little is known about the electrophysiological properties of human cardiac tissues in culture. The present studies were designed to determine the feasibility of maintaining human atrial myocytes in primary culture and to assess changes in Na+ (I(Na)) and K+ (I(to), transient outward, and I(Kur), ultra-rapid delayed rectifier) currents. Within 24 h of culture, cells assumed an ovoid shape, which they maintained for up to 7 days. The voltage dependence, kinetics, and density of I(Na) were unchanged in culture. The activation properties of I(to) (kinetics and voltage dependence) were not altered, but I(to) density (current normalized to cell capacitance) was reduced and inactivation properties were altered (negative shift in voltage dependence and slowed kinetics) in cultured compared with fresh cells. The absolute current amplitude, kinetics, voltage dependence, and 4-aminopyridine sensitivity of I(Kur) were unchanged, but current density was increased. All changes in ionic currents occurred within 24 h of culture and remained stable for the next 4 days. We conclude that human atrial myocytes can be maintained in primary culture, that the qualitative properties of I(Na), I(to), and I(Kur) remain constant but that some quantitative changes occur, and that cultured human atrial myocytes may be valuable for studies of the molecular mechanisms and regulation of cardiac ion channel function in humans.