title: BK Channels in the Vascular System.
abstract: Autoregulation of blood flow is essential for the preservation of organ function to ensure continuous supply of oxygen and essential nutrients and removal of metabolic waste. This is achieved by controlling the diameter of muscular arteries and arterioles that exhibit a myogenic response to changes in arterial blood pressure, nerve activity and tissue metabolism. Large-conductance voltage and Ca(2+)-dependent K(+) channels (BK channels), expressed exclusively in smooth muscle cells (SMCs) in the vascular wall of healthy arteries, play a critical role in regulating the myogenic response. Activation of BK channels by intracellular, local, and transient ryanodine receptor-mediated "Ca(2+) sparks," provides a hyperpolarizing influence on the SMC membrane potential thereby decreasing the activity of voltage-dependent Ca(2+) channels and limiting Ca(2+) influx to promote SMC relaxation and vasodilation. The BK channel α subunit, a large tetrameric protein with each monomer consisting of seven-transmembrane domains, a long intracellular C-terminal tail and an extracellular N-terminus, associates with the β1 and γ subunits in vascular SMCs. The BK channel is regulated by factors originating within the SMC or from the endothelium, perivascular nerves and circulating blood, that significantly alter channel gating properties, Ca(2+) sensitivity and expression of the α and/or β1 subunit. The BK channel thus serves as a central receiving dock that relays the effects of the changes in several such concomitant autocrine and paracrine factors and influences cardiovascular health. This chapter describes the primary mechanism of regulation of myogenic response by BK channels and the alterations to this mechanism wrought by different vasoactive mediators.
authors.affiliation: Nutriflour International Inc. LLC, Norwalk, CT, United States. Electronic address: nutriflourint2015@gmail.com.
authors.forename: G
authors.initials: G
authors.lastname: Krishnamoorthy-Natarajan
authors.affiliation: University of Vermont, Burlington, VT, United States.
authors.forename: M
authors.initials: M
authors.lastname: Koide
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000378:metabolism*; D006801:Humans; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels; D002118:Calcium
keywords: Autoregulation; BK channel; Calcium sparks; Lipids; Myogenic response; Nitric oxide; Phosphorylation; Smooth muscle cell; Vascular diameter