The Na+-activated K+ channel contributes to K+ efflux in Na+-loaded guinea-pig but not rat ventricular myocytes

Activation of the Na+-activated K+ channels (K-Na channels) has been sugges ted to contribute to the ischaemia-induced accumulation of extracellular K (K-e(+)) in the maminalian myocardium. Recent evidence shows that these ch annels are not present in rat ventricular myocytes [9]. We have therefore i nvestigated the effect of raised intracellular Na+ activity (a(Na)(i)) on i ntracellular K+ activity (a(K)(i)) in guinea-pig myocytes, which possess th e channels, and on rat ventricular myocytes which do not. The Na+-activated K+ current was activated by an increase in a(Na)(i) induced by removing ex tracellular Ca2+ and Mg2+ and inhibiting the Na-pump. The a(Na)(i) increase d and the a(K)(i) decreased in both guinea-pig and rat myocytes superfused with Ca2+- and Mg2+-free Tyrode. The new steady-state increase in a(Na)(i) and decline in a(K)(i) were similar in both species. Inhibition of the Na-p ump resulted in an additional increase in a(Na)(i). and decrease in a(K)(i) in both species. However, both the increase in a(Na)(i) and decrease in a( K)(i) Were greater in guinea-pig myocytes and the decline in a(K)(i) in gui nea-pig myocytes followed the development of a large Na+-activated K+ curre nt. When Li+ replaced Na+ in the superfusate the Na+-activated K+ current d id not develop and the fall in a(K)(i) was reduced. In Na+-loaded rat myocy tes, which do not have a Na+-activated K+ current, the decline in a(K)(i) w as reduced and blocked by 2 mM Mg2+ Suggesting that a Mg2+-sensitive non-sp ecific cation channel may be involved in the K+ efflux from rat myocytes [1 2]. These data suggest that K-Na channels are a major route for K+ efflux f rom Na+-loaded guinea-pig myocytes.