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Large-Conductance Calcium-Activated Potassium Channels

  • Hiroaki KumeEmail author
Chapter

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.

Keywords

BKCa channels MaxiK channels STOCs β-adrenergic receptors Muscarinic receptors Patch-clamp techniques Protein Kinase A Protein Kinase G Ca2+ sparks 

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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Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  1. 1.Department of Respiratory Medicine and AllergologyKinki University Faculty of MedicineOsakasayamaJapan

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