Pressure-induced activation of membrane K+ current in rat saphenous artery.
Pressurization of isolated arteries may result in Ca(2+)-dependent contraction and membrane depolarization. Because the open state probability of some vascular muscle K+ channels is augmented by rises in cytosolic Ca2+ and membrane depolarization, we investigated the possibility that increases in intraluminal pressure activate K+ channels in isolated, perfused rat saphenous arteries. Stepwise increases in intraluminal pressure from 5 to 205 mm Hg resulted in increasing, active arterial contraction, measured as smaller diameters in physiological salt solution than in Ca(2+)-free solution. Addition of 10 mM tetraethylammonium to the physiological salt solution to block arterial muscle K+ channels caused progressively greater diameter reductions at pressures above 25 mm Hg. Microelectrode measurements of membrane potential showed that tetraethylammonium depolarized arterial muscle more at 105 mm Hg (16 +/- 1 mV) than at 25 mm Hg (10 +/- 1 mV). The sensitivity of K+ current to tetraethylammonium was also demonstrated in patch-clamped vascular muscle cells from the same arteries. Peak whole-cell K+ current was suppressed 47% and 79% by 1 and 10 mM tetraethylammonium, respectively. This same current was enhanced 3.6-fold by the Ca2+ ionophore A23187 (10 microM), suggesting a Ca2+ dependence. We conclude that increases in intraluminal pressure progressively activate tetraethylammonium-sensitive K+ channels in the arterial muscle membrane. This can serve as a negative feedback mechanism to limit pressure-induced arterial constriction.
Berczi
V
V
Department of Physiology, Medical College of Wisconsin, Milwaukee 53226.
Stekiel
W J
WJ
Contney
S J
SJ
Rusch
N J
NJ
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D001794:Blood Pressure; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004594:Electrophysiology; D004730:Endothelium, Vascular / Q000502:physiology; D007866:Leg / Q000098:blood supply*; D008566:Membranes / Q000502:physiology; D011188:Potassium / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013563:Sympathectomy, Chemical; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D014662:Vasoconstrictor Agents; D000001:Calcimycin; D019789:Tetraethylammonium; D011188:Potassium; D002118:Calcium