Effects of intracellular N+, M2+ and metabolites on C2+-activated K+ channels in pulmonary and ear arterial smooth muscle cells of the rabbit.

Hypoxic pulmonary vasoconstriction (HPV) is an important mechanism for matching the ventilation/perfusion ratio in the lung, but the signal transduction pathway through which hypoxia induces vasoconstriction remains unclear. We hypothesized that the decrease in K+ current induced by hypoxia is a key mechanism for HPV, and examined the effects of the substances which are expected to accumulate during hypoxia on the activity of large conductance Ca2+-activated K+ (BKCa) channels. Pulmonary and ear arterial smooth muscle cells were isolated from the rabbit using enzymatic digestion, and large conductance Ca2+-activated K+ current (IBK,Ca) was recorded in symmetrical K+ concentrations using the inside-out mode of the patch-clamp technique. Increasing the Na+ concentration on the intracellular side suppressed IBK,Ca dose dependently: 4.6, 20.9, 35.5 and 44.6 % reduction with 4, 8, 12 and 16 mM Na+, respectively. Mg2+ also reduced IBK,Ca, and the maximum reduction was obtained at 0.5 mM. Lactate, adenosine, ADP and ATP did not significantly affect IBK,Ca. There was no difference between pulmonary and ear arterial smooth muscle cells in their response to the above substances; this finding rules out modulation of BKCa channels by the various factors thought to accumulate during hypoxia as a major mechanism involved in the decrease in the K+ conductance of pulmonary arteries in hypoxia.