Differential segmental activation of Ca2+ -dependent CI-and K+ channels in pulmonary arterial myocytes.

ABSTRACT

Differential segmental distribution of electrophysiologically distinct myocytes helps to explain the variability of the pulmonary arteries to vasoactive agents. We have studied whether Ca2+ -dependent CI- (CICa) and K+ (KCa) channels are activated differentially in enzymatically dispersed conduit and resistance myocytes. We measured cytosolic [Ca2+] and the changes of membrane current and potential elicited by spontaneous or agonist-induced Ca2+ oscillations. Conduit arteries contained a heterogeneous cell population with a variable mixture of KCa and CICa conductances. Resistance arteries contained a more homogeneous cell population with predominance of CICa channel activation. The relation between KCa and CICa conductances in a given conduit myocyte determines the size of the V(m)change in response to a rise of cytosolic [Ca2+]. Conduit myocytes tend to hyperpolarize towards the K+ equilibrium potential (approximately - 90 m V). In resistance myocytes, release of Ca2+ from stores activates CI Cachannels and brings Vm to a value close to the chloride equilibrium potential (approximately - 20 or - 30 m V) thus favouring opening of Ca2+ channels and Ca2+ influx. In resistance vessels CICachannels contribute to link agonist-induced Ca2+ release from stores and membrane depolarization, thus permitting protracted vasoconstriction.