potassium large conductance calcium-activated channel, subfamily M, beta member 1 Synonyms: SLO-BETA hslo-beta K(VCA)beta KCNMB1. Symbol: Kcnmb1
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 , Vergara , Kaczorowski ). 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 , Behrens ). 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 ). 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 ).
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.
Kcnmb1 : potassium large conductance calcium-activated channel, subfamily M, beta member 1
A protein complex that forms a transmembrane channel through which potassium ions may cross a cell membrane in response to changes in membrane potential.
Double layer of lipid molecules that encloses all cells, and, in eukaryotes, many organelles; may be a single or double lipid bilayer; also includes associated proteins.
integral to membrane
Penetrating at least one phospholipid bilayer of a membrane. May also refer to the state of being buried in the bilayer with no exposure outside the bilayer. When used to describe a protein, indicates that all or part of the peptide sequence is embedded in the membrane.
At the molecular level, the BK channel in vascular smooth muscle is formed by
an ion-conducting α subunit (Meera ) and a regulatory β1 subunit, encoded by KCNMB1
(McManus , Tanaka , Orio ).
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 )
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 ). 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 , Toro ).
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 ). 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 , Orio , Knaus , Meera , Brenner , Pluger ).
KCNMB1 gene might be involved in the pathogenesis of human
hypertension. (Fernandez-Fernandez )
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 )