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Regulation of BK Channel Activity by Cholesterol and Its Derivatives

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Book cover Cholesterol Modulation of Protein Function

Part of the book series: Advances in Experimental Medicine and Biology ((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.

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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

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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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Authors and Affiliations

  1. The University of Tennessee Health Science Center, Memphis, TN, USA

    Anna N. Bukiya & Alex M. Dopico

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  1. Anna N. Bukiya
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  2. Alex M. Dopico
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Correspondence to Anna N. Bukiya .

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  1. Department of Chemistry, University of Illinois, Chicago, IL, USA

    Avia Rosenhouse-Dantsker

  2. The University of Tennessee Health Science Center, Memphis, TN, USA

    Anna N. Bukiya

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Bukiya, A.N., Dopico, A.M. (2019). Regulation of BK Channel Activity by Cholesterol and Its Derivatives. In: Rosenhouse-Dantsker, A., Bukiya, A.N. (eds) Cholesterol Modulation of Protein Function. Advances in Experimental Medicine and Biology, vol 1115. Springer, Cham. https://doi.org/10.1007/978-3-030-04278-3_3

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