Nitric oxide (NO) is an endogenous vasodilator and inhaled NO is a promising therapeutic agent for the treatment of pulmonary hypertension. However, NO's mechanism of action is not completely understood. Previous studies have shown that NO increases intracellular levels of cyclic guanosine 3',5'-monophosphate (cGMP) and that leads to activation of calcium-gated potassium channels in vascular smooth muscle cells. Resulting cell membrane hyperpolarization causes vasorelaxation. The potassium channel activation by NO is inhibited by a blockade of cyclic nucleotide-dependent protein kinases, suggesting a key role of these enzymes in NO-induced vasodilation. To further examine this mechanism, we tested the hypothesis that pharmacological stimulation of the cGMP-dependent protein kinase will simulate the activating effect of NO on potassium channels. Indeed, we found that (Sp)-guanosine cyclic 3’,5'-phosphorothioate (1 /¿M), a selective activator of the cGMP-dependent protein kinase, dramatically increased potassium currents measured by the whole-celi patch clamp technique in freshly dispersed pulmonary artery smooth muscle cells. These currents were inhibited by an inhibitor of calcium-gated potassium channels, charybdotoxin. Our results support the hypothesis that the effect of NO on potassium channels is mediated by the cGMP-dependent protein kinase.
We examined the effect of ethanol on single potassium channels derived from plasma membranes of bovine tracheal smooth muscles. The observed potassium channels had a conductance of 296±31 pS (mean ± S.D.) in symmetrical 250 mmol/l KCl solutions, and exhibited a voltage- and Ca2+-dependence similar to BKCa channels. Ethanol at 50, 100 and 200 mM concentrations increased the probability of open potassium channels to 112±5, 127±7 and 121±13% (mean ± S.E.M.), respectively. It is suggested that increased activity of the BKCa channels by ethanol hyperpolarizes the plasma membrane and thus may contribute to relaxation of tracheal smooth muscle., V. Komínková, M. Magová, A. Mojžišová, Ľ. Máleková, K. Ondriaš., and Obsahuje bibliografii