ATP-sensitive K+ channels regulate resting potential of pulmonary arterial smooth muscle cells.
ATP-sensitive K+ (KATP) channels have been proposed to be the target for hyperpolarizing vasodilators. However, the existence of a whole cell KATP 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 KATP-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 (less than 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 plays an important role in the maintenance of the resting potential in arterial muscle.
Clapp
L H
LH
Department of Pharmacology, United Medical School, St. Thomas's Hospital, London, United Kingdom.
Gurney
A M
AM
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D019806:Cromakalim; D004594:Electrophysiology / Q000379:methods; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011651:Pulmonary Artery / Q000502:physiology*; D011758:Pyrroles / Q000494:pharmacology; D011817:Rabbits; D014665:Vasodilator Agents / Q000494:pharmacology
D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; C029273:P(3)-1-(2-nitro)phenylethyladenosine 5'-triphosphate; D000255:Adenosine Triphosphate; D005905:Glyburide