ATP-SENSITIVE K+ CHANNELS REGULATE RESTING POTENTIAL OF PULMONARY ARTERIAL SMOOTH-MUSCLE CELLS

ATP-sensitive K+ (K(ATP)) channels have been proposed to be the target for hyperpolarizing vasodilators. However, the existence of a whole cell K(ATP) current that can regulate membrane potential has not been demonstrated in vascular muscle. Using the patch-clamp technique, we have examined the effects of varying intracellular ATP on membrane potential and currents in isolated rabbit pulmonary arterial smooth muscle cells. With 1 mM ATP in the pipette, cells had a mean resting potential of -55 mV. When ATP was omitted, the resting potential became significantly more hyperpolarized (-70 mV) and the depolarizing response to the K(ATP)-channel blocker, glibenclamide, was potentiated. In contrast, the hyperpolarizing effect of lemakalim was reduced. These hyperpolarized resting potentials were associated with increased activity of a basal, glibenclamide-sensitive time-independent K+ current. Furthermore, flash photolysis of ATP, 3-O-[1(4,5-dimethoxy-2-nitrophenyl)ethyl] ester, disodium salt ("caged ATP") in ATP-depleted cells caused rapid depolarization (<1 s) and block of the background K+ current. Our results are consistent with the idea that intracellular ATP can directly modulate the resting potential by inhibition of K+ channels. We propose that this ATP-sensitive K+ current play an important role in the maintenance of the resting potential in arterial muscle.