NADH AND NAD MODULATES CA2-ACTIVATED K+ CHANNELS IN SMALL PULMONARY ARTERIAL SMOOTH-MUSCLE CELLS OF THE RABBIT()

We have investigated the effect of NADH and NAD on the gating of large conductance Ca2+-activated K(K-Ca) channels in arterial smooth muscle cells isolated from small pulmonary artery(outer diameter <300 mu m) and ear artery, using the patch clamp technique. In the inside-out con figuration, intracellularly applied 2 mM NADH inhibited the activity o f K-Ca channels in pulmonary arterial smooth muscle cells, while it ha d no significant effect on ear arterial smooth muscle cells. On the ot her hand, 2 mM NAD increased the opening of K-Ca channels in pulmonary arterial smooth muscle cells. The effects of another intracellular re dox couple, glutathione(GSH) and glutathione disulfide(GSSG) were also dependent on their redox potentials. GSH(S mM) inhibited K-Ca channel s activity, while GSSG(S mM) increased the activity of pulmonary arter ial smooth muscle cells. It could be concluded that the modulation of K-Ca channels by intracellular redox state contributes, at least in pa rt, to the hypoxic suppression of outward current in pulmonary arteria l smooth muscle cells.