BKβ1

Description: potassium large conductance calcium-activated channel, subfamily M, beta member 1
Gene: Kcnmb1
Alias: SLO-BETA, hslo-beta, K(VCA)beta, KCNMB1, BKB1

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Introduction

BK channels are broadly expressed, and have functional roles in vascular smooth muscle as well as other tissues including skeletal muscle, neurons, kidney and secretory cells (Sah [1171], Vergara [1100], Kaczorowski [1172]). The functional diversity required for the tissue-specific roles of BK channels may be created in part by association with accessory b-subunits. A family of four BK b-subunits has been identified (Brenner [1169], Behrens [1173]). Each family member has a different tissue distribution and different effects on BK channel pharmacology and activation gating. The b1-subunit is enriched in smooth muscle and purifies with the BK pore-forming subunit (knaus [1172]). In expression systems, the b1 subunit confers an increased calcium sensitivity, slows gating kinetics and increases the sensitivity to the agonist dehydrosoyasaponin (DHS-1) (McManus [1163]).

KCNMB1 (also known as SLO-BETA; hslo-beta; K(VCA)beta) encodes the BkB1 channel. MaxiK channels are large conductance, voltage and calcium-sensitive potassium channels which are fundamental to the control of smooth muscle tone and neuronal excitability. MaxiK channels can be formed by 2 subunits: the pore-forming alpha subunit and the product of this gene, the modulatory beta subunit. Intracellular calcium regulates the physical association between the alpha and beta subunits.

http://www.ncbi.nlm.nih.gov/gene/3779

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Gene

Species	NCBI gene ID	Chromosome	Position
Human	3779	5	14696
Mouse	16533	11	10686
Rat	29747	10	57314

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Transcript

Species	NCBI accession	Length (nt)
Human	NM_004137.4	4742
Mouse	NM_031169.4	4188
Rat	NM_019273.1	1278

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Protein Isoforms

Species	Uniprot ID	Length (aa)
Human	Q16558	191
Mouse	Q8CAE3	191
Rat	P97678	191

Isoforms

Transcript

Length (nt)

Protein

Length (aa)

Variant

Isoform

Known

NM_019273.1

1278

NP_062146.1

191

Predicted

XM_039085796.1

2186

XP_038941724.1

189

transcript variant X2

isoform X2

XM_039085797.1

4670

XP_038941725.1

146

transcript variant X3

isoform X3

XM_006246089.4

4561

XP_006246151.1

191

transcript variant X1

isoform X1

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Post-Translational Modifications

PTM

Position

Type

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Structure

At the molecular level, the BK channel in vascular smooth muscle is formed by an ion-conducting α subunit (Meera [1164]) and a regulatory β1 subunit, encoded by KCNMB1 (McManus [1162], Tanaka [1163], Orio [540]).

BKβ1 predicted AlphaFold size

Species	Area (Å²)	Reference
Human	3080.55	source
Mouse	3444.43	source
Rat	2854.14	source

Methodology for AlphaFold size prediction and disclaimer are available here

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Expression and Distribution

Using sensitivity to DHS-1 as a probe for BK a/b1 subunits, it has been shown that human coronary artery smooth muscle is enriched for a/b1-assembled BK channels, and that these channels are more calcium sensitive than BK channels in other tissues where the b1 subunit is not expressed. (Tanaka [1163])

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Function

The control of arterial tone depends on a calcium signal in the vascular smooth muscle, mainly provided by the influx of Ca2+ via voltage-gated channels and its release from intracellular stores (Jaggar [1165]). A key element in the control of the vascular tone is the large-conductance, Ca2+- and voltage-dependent K+ (BK) channel, which couples local increases in intracellular Ca2+ to aug- mented channel activity and vascular relaxation (Jaggar [1165], Toro [1166]). In smooth muscle, an increase in BK channel activity is induced by local releases of Ca2+ from the sarcoplasmic reticulum (“Ca2+ sparks”) that lead to hyperpolarization of the membrane and prevention of further influx of Ca2+ (Jaggar [1165]). This negative-feedback mechanism is finely tuned by the presence of the β1 subunit of the BK channel, which increases channel sensitivity to Ca2+ (McManus [1162], Orio [540], Knaus [1167], Meera [1168], Brenner [1169], Pluger [1170]).

KCNMB1 gene might be involved in the pathogenesis of human hypertension. (Fernandez-Fernandez [243])

Targeted deletion of the gene for the b1 subunit leads to a decrease in the calcium sensitivity of BK channels, a reduction in functional coupling of calcium sparks to BK channel activation, and increases in arterial tone and blood pressure. The b1 subunit of the BK channel, by tuning the channel's calcium sensitivity, is a key molecular component in translating calcium signals to the central physiological function of vasoregulation. (Brenner [1169])

References

243

Gain-of-function mutation in the KCNMB1 potassium channel subunit is associated with low prevalence of diastolic hypertension.
J. Clin. Invest., 2004 Apr , 113 (1032-9).

540

Orio P et al. New disguises for an old channel: MaxiK channel beta-subunits.
News Physiol. Sci., 2002 Aug , 17 (156-61).

1100

Vergara C et al. Calcium-activated potassium channels.
Curr. Opin. Neurobiol., 1998 Jun , 8 (321-9).

1162

McManus OB et al. Functional role of the beta subunit of high conductance calcium-activated potassium channels.
Neuron, 1995 Mar , 14 (645-50).

1163

Tanaka Y et al. Molecular constituents of maxi KCa channels in human coronary smooth muscle: predominant alpha + beta subunit complexes.
J. Physiol. (Lond.), 1997 Aug 1 , 502 ( Pt 3) (545-57).

1164

Meera P et al. Large conductance voltage- and calcium-dependent K+ channel, a distinct member of voltage-dependent ion channels with seven N-terminal transmembrane segments (S0-S6), an extracellular N terminus, and an intracellular (S9-S10) C terminus.
Proc. Natl. Acad. Sci. U.S.A., 1997 Dec 9 , 94 (14066-71).

1165

Jaggar JH et al. Calcium sparks in smooth muscle.
Am. J. Physiol., Cell Physiol., 2000 Feb , 278 (C235-56).

1166

Toro L et al. Maxi-K(Ca), a Unique Member of the Voltage-Gated K Channel Superfamily.
News Physiol. Sci., 1998 Jun , 13 (112-117).

1167

Knaus HG et al. Primary sequence and immunological characterization of beta-subunit of high conductance Ca(2+)-activated K+ channel from smooth muscle.
J. Biol. Chem., 1994 Jun 24 , 269 (17274-8).

1168

Meera P et al. A calcium switch for the functional coupling between alpha (hslo) and beta subunits (Kv,cabeta) of maxi K channels.
FEBS Lett., 1996 Apr 29 , 385 (127-8).

1169

Brenner R et al. Vasoregulation by the beta1 subunit of the calcium-activated potassium channel.
Nature, 2000 Oct 19 , 407 (870-6).

1170

Plüger S et al. Mice with disrupted BK channel beta1 subunit gene feature abnormal Ca(2+) spark/STOC coupling and elevated blood pressure.
Circ. Res., 2000 Nov 24 , 87 (E53-60).

1171

Sah P Ca(2+)-activated K+ currents in neurones: types, physiological roles and modulation.
Trends Neurosci., 1996 Apr , 19 (150-4).

1172

Kaczorowski GJ et al. High-conductance calcium-activated potassium channels; structure, pharmacology, and function.
J. Bioenerg. Biomembr., 1996 Jun , 28 (255-67).

1173

Behrens R et al. hKCNMB3 and hKCNMB4, cloning and characterization of two members of the large-conductance calcium-activated potassium channel beta subunit family.
FEBS Lett., 2000 May 26 , 474 (99-106).

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To cite this page: [Contributors] Channelpedia https://channelpedia.epfl.ch/wikipages/72/ , accessed on 2024 Dec 21

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