Alteration of arterial smooth muscle potassium channel composition and BKCa current modulation in hypertension.
We investigated K+ currents and their regulation by the sarcoplasmic reticulum in mesenteric arterial smooth muscle cells of the spontaneously hypertensive rat (SHR). Using perforated patch-clamp technique, we found the overall K+ current density was significantly lower in adult SHR compared to adult Wistar-Kyoto rats (WKY). The K+ currents were almost exclusively of large-conductance Ca2+-dependent (BK(Ca)) variety in SHR, but largely of voltage-gated (Kv) variety in WKY. Western blot assay showed parallel findings. These differences were not observed in pre-hypertensive rats. Depleting the intracellular Ca2+ store inhibited the K+ currents in adult SHR. Ryanodine augmented the K+ current at 1 microM, but suppressed it at 10 microM; 2-aminoethoxydiphenyl borate demonstrated concentration-dependent inhibition. We conclude that an alteration of membrane K+ channel composition has resulted in lower overall K+ current density. The changes in K+ current type may indicate an underlying defect in Ca2+-handling that predisposes smooth muscle cells to the hypertensive phenotype.
Zhang
Yongde
Y
Department of Medicine, McMaster University, Canada.
Gao
Yu-Jing
YJ
Zuo
Jianmin
J
Lee
Robert M K W
RM
Janssen
Luke J
LJ
D000818:Animals; D015153:Blotting, Western; D001896:Boron Compounds / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000503:physiopathology*; D007211:Indoles / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008638:Mesenteric Arteries / Q000166:cytology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D019789:Tetraethylammonium / Q000494:pharmacology; D013997:Time Factors
D001896:Boron Compounds; D007211:Indoles; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D012433:Ryanodine; D002110:Caffeine; D019789:Tetraethylammonium; C109986:2-aminoethoxydiphenyl borate; D002118:Calcium; C000543:cyclopiazonic acid