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Regulation of BK Channel Activity by Cholesterol and Its Derivatives

  • Anna N. BukiyaEmail author
  • Alex M. Dopico
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1115)

Abstract

Cholesterol (CLR) is an essential structural lipid in the plasma membrane of animal cells. In addition, CLR has been widely recognized as a critical modulator of protein function, including ion channels. Voltage- and Ca2+-gated K+ (BK) channels control a wide variety of physiological processes, including cell excitability, smooth muscle contractility, sensory perception, neurotransmitter release, and hormone secretion. Thus, disruption of BK currents has been implicated in the pathophysiology of prevalent human diseases. The current chapter reviews the literature documenting CLR modulation of BK channel function at a variety of levels ranging from organ systems to artificial lipid bilayers. We discuss the use of CLR isomers and structural analogs as a tool to help in discerning the mechanisms underlying CLR-driven modification of BK current. The chapter is finalized with an overview of the phenomenology and potential mechanisms that govern CLR control over the alcohol (ethyl alcohol, ethanol) sensitivity of BK channels. Studies on CLR regulation of BK currents may ultimately pave the way for novel therapeutic approaches to combat prevalent pathophysiological and morbid conditions.

Keywords

MaxiK channel Alcohol Cerebral artery High cholesterol diet Hypercholesterolemia 

Abbreviations

BK

Voltage- and Ca2+-gated K+ (channels)

CLR

Cholesterol

CTD

Cytosolic tail domain

LDL

Low-density lipoprotein

LRRC

Leucine-rich repeat-containing (protein)

MβCD

Methyl-β-cyclodextrin

PGD

Pore-gate domain

RCK

Regulator of conductance of potassium (domain)

SPM

Sphingomyelin

TM

Transmembrane

VSD

Voltage-sensing domain

Notes

Acknowledgements

This work was supported by National Institute of Alcohol Abuse and Alcoholism and National Heart and Lung Institute grants R37 AA11560 (AMD), R01 HL104631 (AMD), and R01 AA023764 (ANB).

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.The University of Tennessee Health Science CenterMemphisUSA

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