Regulation of membrane potential and diameter by voltage-dependent K+ channels in rabbit myogenic cerebral arteries.
The hypothesis that voltage-dependent K+ channels are involved in the regulation of arterial smooth muscle membrane potential and blood vessel diameter was tested by examining the effects of inhibitors [4-aminopyridine (4-AP) and 3,4-diaminopyridine (3,4-DAP)] of voltage-dependent K+ channels on the membrane potential and diameter of pressurized small (100- to 300-microns diam) cerebral arteries from rabbit. In response to graded elevations in transmural pressure (20-100 mmHg), the membrane potential of smooth muscle cells in these arteries depolarized and the arteries constricted. 4-AP (1 mM) and 3,4-DAP (1 mM) depolarized cerebral arteries by 19 and 21 mV, respectively, when they were subjected to a transmural pressure of 80 mmHg. 3-Aminopyridine (3-AP, 1 mM), which is a relatively poor inhibitor of voltage-dependent K+ channels, depolarized smooth muscle cells in the arteries by 1 mV. 4-AP and 3,4-DAP constricted pressurized (to 80 mmHg) cerebral arteries. 3-AP had little effect on arterial diameter. 4-AP increased the arterial constriction to transmural pressure over a wide range of pressures (40-90 mmHg). The effects of 4-AP and 3,4-DAP on membrane potential and diameter were not prevented by inhibitors of calcium channels, calcium-activated K+ channels, ATP-sensitive K+ channels, inward rectifier K+ channels, blockers of adrenergic, serotonergic, muscarinic, and histaminergic receptors, or removal of the endothelium. These results suggest that voltage-dependent K+ channels are involved in the regulation of membrane potential and response of small cerebral arteries to changes in intravascular pressure.
Knot
H J
HJ
Department of Pharmacology, University of Vermont, Colchester 05446-2500, USA.
Nelson
M T
MT
D015761:4-Aminopyridine / Q000031:analogs & derivatives / Q000494:pharmacology; D000077770:Amifampridine; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002536:Cerebral Arteries / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004594:Electrophysiology; D008564:Membrane Potentials / Q000187:drug effects; D009129:Muscle Tonus; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D011817:Rabbits; D014661:Vasoconstriction / Q000502:physiology
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D015761:4-Aminopyridine; D000077770:Amifampridine