Aminopyridine inhibition and voltage dependence of K+ currents in smooth muscle cells from cerebral arteries.
Voltage-dependent K+ currents were characterized using the patch-clamp technique in smooth muscle cells isolated from rabbit cerebral (basilar) arteries. This study focused on the voltage dependence and the pharmacology of these K+ currents, since this information will be useful for the investigation of the role of the voltage-dependent K+ channels in arterial function. Currents through Ca(2+)-activated K+ (KCa) channels were minimized by buffering intracellular Ca2+ to low levels and by blockers (tetraethylammonium and iberiotoxin) of these channels. Membrane depolarization increased K+ currents, independent of changes in the driving force for K+ movement. With 140 mM internal and external K+, activation of K+ currents by membrane depolarization was half maximal at about -10 mV and increased as much as e-fold per 11 mV. Inactivation also depended on voltage, with a midpoint at -44 mV. 3,4-Diaminopyridine (3,4-DAP),4-aminopyridine(4-AP),3-amino-pyridine(3-AP), and 2-aminopyridine (2-AP) inhibited voltage-dependent K+ currents. At 0 mV, 3,4-DAP, 4-AP, 3-AP, and 2-AP (5 mM) inhibited the K+ currents by 84, 66, 36, and 8%, respectively. Phencyclidine (100 microM) inhibited the current by 53% at 0 mV. Steady-state whole cell currents through these channels were measured at physiological membrane potentials. At -40 mV, 4-AP (5 mM) reduced the steady-state outward current by 2.5 pA. These results are consistent with the idea that voltage-dependent K+ channels are involved in the regulation of the membrane potential of arterial smooth muscle.
Robertson
B E
BE
Department of Pharmacology, University of Vermont, Colchester 05446-2500.
Nelson
M T
MT
D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D002536:Cerebral Arteries / Q000378:metabolism; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D010622:Phencyclidine / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D011817:Rabbits; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D015761:4-Aminopyridine; D010622:Phencyclidine