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Large-Conductance Calcium-Activated Potassium Channels

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Calcium Signaling In Airway Smooth Muscle Cells

Abstract

Large-conductanceCa2+-activated K+ (BKCa, MaxiK) channels are abundantly distributed on the cell membrane and ubiquitously expressed in a variety of tissues except cardiac muscle. These channels have a conductance of approximately 250 pS and are intracellular Ca2+- and membrane potential-sensitive. Activation of these channels causes membrane hyperpolarization mediated by an increase in outward K+ currents, leading to a reduction in tension in smooth muscle such as vessels and airways. The BKCa channels are a tetramer of a pore-forming α-subunit encoded by a single gene (Slo, KCNMA1) associated with modulatory β-subunits (KCNMB1-4). The α-subunit consists of a transmembrane (TM) domain-sensing membrane potential and conducting ion, and a cytoplasmic domain-sensing Ca2+. The β-subunits comprise two TMs, and their expression is tissue specific. In smooth muscle cells, the BKCa channels are markedly activated due to increased local Ca2+ concentrations via Ca2+ release from the sarcoplasmic reticulum (Ca2+ sparks). The coupling of Ca2+ sparks to hundreds of BKCa channels causes spontaneous outward currents (STOCs), leading to relaxation via membrane hyperpolarization. The activity and expression of the BKCa channels are modulated by a variety of factors such as phosphorylation (e.g., protein kinase A, protein kinase G) and other metabolites (e.g., reactive oxygen species, estrogen, nitric oxide). Therefore, altered BKCa channels play a key role in vital body functions (e.g., development, pregnancy) and diseases (e.g., hypertension, diabetes). These channels may be a therapeutic target for a variety of diseases.

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Abbreviations

20-HETE:

20-Hydroxyeicosatetraenoic acid

4-AP:

4-aminopyridine

ACh:

Acetylcholine

AF-DX 116:

11-[[2-[(Diethylamino)methyl]-1-piperidinyl]acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1, 4]benzodiazepin-6-one

ATP:

Adenosine triphosphate

BKCa channels:

Large-conductance calcium-activated potassium channels

cAMP:

Cyclic adenosine monophosphate

CCh:

Carbachol

cGMP:

Cyclic guanosine monophosphate

ChTX:

Charybdotoxin

EETs:

Epoxyeicosatrienoic acids

GDP-β-S:

Guanosine 5′-O-(2-thio-diphoshate)

Gi :

Inhibitory G protein of adenylyl cyclase

Gs :

Stimulatory G protein of adenylyl cyclase

GTP:

Guanosine triphosphate

GTP-γ-S:

Guanosine 5′-O-(3-thiotriphosphate)

IbTX:

Iberiotoxin

IP3 :

Inositol triphosphate

MCh:

Methacholine

NO:

Nitric oxide

nPo:

Open probability of ion channels

PKA:

Protein kinase A

PKC:

Protein kinase C

PKG:

Protein kinase G

ROS:

Reactive oxygen species

RyR:

Ryanodine receptors

SR:

Sarcoplasmic reticulum

STOCs:

Spontaneous outward currents

TEA:

Tetraethylammonium

αs :

α-subunit of Gs

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  1. Department of Respiratory Medicine and Allergology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, 589-8511, Japan

    Hiroaki Kume M.D., Ph.D.

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  1. Hiroaki Kume M.D., Ph.D.
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Correspondence to Hiroaki Kume M.D., Ph.D. .

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  1. Albany Medical College Center for Cardiovascular Sciences, Albany, New York, USA

    Yong-Xiao Wang

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Kume, H. (2014). Large-Conductance Calcium-Activated Potassium Channels. In: Wang, YX. (eds) Calcium Signaling In Airway Smooth Muscle Cells. Springer, Cham. https://doi.org/10.1007/978-3-319-01312-1_4

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