BIOPHYSICAL PROPERTIES OF CA2+-ACTIVATED AND MG-ATP-ACTIVATED K+ CHANNELS IN PULMONARY ARTERIAL SMOOTH-MUSCLE CELLS ISOLATED FROM THE RAT

A novel class of Ca2+-activated K+ channel, also activated by Mg-ATP, exists in the main pulmonary artery of the rat. In view of the sensitivity of these ''K-Ca,K-ATP'' channels to such charged intermediates it is possible that they may be involved in regulating cellular responses to hypoxia. However, their electrophysiological profile is at present unknown. We have therefore characterised the sensitivity of K-Ca,K-ATP channels to voltage, intracellular Ca2+ ([Ca2+](i)) and Mg-ATP. They have a conductance of 245 pS in symmetrical K+ and are approximately 20 times more selective for K+ ions than Na+ ions, with a K+ permeability (P-kappa) of 4.6x10(-13)cm s(-1). Ca2+ ions applied to the intracellular membrane surface of K-Ca,K-ATP channels causes a marked enhancement of their activity. This activation is probably the result of simultaneous binding of at least two Ca2+ ions, determined using Hill. analysis, to the channel or some closely associated protein. This results in a shift of the voltage activation threshold to more hyperpolarized membrane potentials. The activation of K-Ca,K-ATP channels by Mg-ATP has an EC(50) of approximately 50 mu M. Although the EC(50) is unaffected by [Ca2+](i), channel activation by Mg-ATP is enhanced by increasing [Ca2+](i). One possible interpretation of these data is that Mg-ATP increases the sensitivity of K-Ca,K-ATP channels to Ca2+. It is therefore possible that under hypoxic conditions, where lower levels of Mg-ATP may be encountered, the sensitivity of K-Ca,K-ATP channels to Ca2+ and therefore voltage is reduced. This would tend to induce a depolarising influence, which would favour the influx of Ca2+ through voltage-activated Ca2+ channels, ultimately leading to increased vascular tone.