title: Function of BKCa channels is reduced in human vascular smooth muscle cells from Han Chinese patients with hypertension.
abstract: Chronic hypertension is associated with an impaired vascular relaxation caused by an increased vascular tone; however, the underlying mechanisms are not fully understood in human patients. The present study was to investigate whether large-conductance Ca(2+)- and voltage-activated K(+) (BK(Ca)) channels are involved in dysfunctional relaxation of artery in Han Chinese patients with hypertension using the perforated patch clamp, inside-out single-channel, and macromembrane patch recording techniques to determine whole-cell current, spontaneous transient outward current, open probability, and Ca(2+) sensitivity and the reverse transcription polymerase chain reaction and Western blot analysis to examine the gene and protein expression of α-subunit (KCa1.1) and β1-subunit (KCNMB1) of BK(Ca) channels in isolated human vascular smooth muscle cells and mesenteric arteries from normotensive and hypertensive patients. It was found that whole-cell current density, spontaneous transient outward current, and Ca(2+) sensitivity, but not single-channel open probability and slope conductance, were significantly decreased in vascular smooth muscle cells from patients with hypertension. Interestingly, mRNA and protein levels of KCNMB1, but not KCa1.1, were reduced in the arterial tissue from patients with hypertension. These results demonstrate for the first time that whole-cell current, spontaneous transient outward current, and Ca(2+) sensitivity of BK(Ca) channels are reduced in human vascular smooth muscle cells, which resulted from downregulation of β1-subunit of the channel. This may account, at least in part, for the dysfunction of artery relaxation in Han Chinese patients with primary hypertension.
authors.affiliation: Key Laboratory of Medical Electrophysiology, Ministry of Education of China, and the Institute of Cardiovascular Research, Luzhou Medical College, Luzhou, Sichuan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: Peng-Yun
authors.initials: PY
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
authors.forename: Liang
authors.initials: L
authors.lastname: Mao
authors.forename: Jing
authors.initials: J
authors.lastname: Wen
authors.forename: Xiao-Qiu
authors.initials: XQ
authors.lastname: Tan
authors.forename: Zhi-Fei
authors.initials: ZF
authors.lastname: Liu
authors.forename: Xiao-Rong
authors.initials: XR
authors.lastname: Zeng
mesh_terms: D044466:Asian People; D002118:Calcium / Q000378:metabolism; D002681:China; D006801:Humans; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D008564:Membrane Potentials / Q000502:physiology; D008638:Mesenteric Arteries / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism* / Q000503:physiopathology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels; D002118:Calcium