Function of BK _Ca Channels Is Reduced in Human Vascular Smooth Muscle Cells From Han Chinese Patients With Hypertension

Abstract

It is well known that chronic hypertension is associated with increased morbidity and mortality from stroke, coronary artery disease, congestive heart failure, renal disease, and so on.1,2 Arterial tone is persistently increased as a result of malfunction of vessel relaxation in chronic hypertension.2 It is well recognized that arterial tone is regulated by functional balance of the ion channels responsible for cellular depolarization and hyperpolarization. The increased arterial tone is mainly related to depolarization of smooth muscle, which may have resulted from dysfunction of ion channels responsible for cell membrane hyperpolarization. 3 The membrane depolarization activates voltage-dependent l-type Ca 2+ channels, induces an increase in Ca 2+ influx and global intracellular Ca 2+ level, and causes vessel constriction. 4,5 It is believed that large-conductance Ca 2+ -activated K + (BK Ca ) channels play an important role in hyperpolarization of vascular smooth muscle cells (VSMCs).6 BK Ca channels are activated by intracellular local Ca 2+ release events through ryanodine receptors (Ca 2+ sparks) from the sarcoplasmic reticulum and subsequently induce a hyperpolarization that opposes vasoconstriction. 6-8The Ca 2+ sparks are highly localized and short-lived Ca 2+ transients, which is a local Ca 2+ signaling to induce spontaneous transient outward currents (STOCs) in VSMCs and neurons, and mediate different physiological functions. 8,9 In VSMCs, functional coupling of sparks to STOCs hyperpolarizes the membrane potential, which in turn closes the voltage-dependent l-type Ca 2+ channels, decreases global [Ca 2+ ] i , and induces vascular relaxation. 7 Studies from animal models demonstrated that a reduced activity of Ca 2+ sparks and STOCs is involved in an increase of vascular tone in hypertension. [10][11][12] However, little information is available in literature regarding BK Ca channel activity in human arterial cells/tissue from patients with hypertension. The present study was therefore to investigate whether BK Ca activity is altered in VSMCs isolated from mesentery arterial tissues of Han Chinese patients with hypertension using approaches of electrophysiology and molecular biology.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 ...

High-fat diet-induced obesity alters nitric oxide-mediated neuromuscular transmission and smooth muscle excitability in the mouse distal colon

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Expression and alteration of BKCa channels in the sphincter of Oddi's from rabbits with hypercholesterolemia

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