Logged in as a Visitor.
potassium large conductance calcium-activated channel, subfamily M beta member 3
Until 1999, only one beta subunit of BK (MaxiK) channels was known at the molecular level. This subunit (now known as the Beta-1-subunit) accounted mainly for MaxiK properties in vascular smooth muscle cells (VSMCs), where it is highly expressed. In the following years, three more beta subunits have been cloned and characterized. (Orio )
KCNMB3 (also known as HBETA3; KCNMB2; KCNMBL; BKBETA3; SLOBETA3) encodes BKB3, potassium large conductance calcium-activated channel (subfamily M) beta member 3. 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 modulatory beta subunit. BKB3 may partially inactivate or slightly decrease the activation time of MaxiK alpha subunit currents. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 22.
The b3-subunit (BKB3) was cloned from human EST databases and is phylogenetically more related to b2 than to b1 (Uebele ). There are four splice variants (BKB3a-d), whose differences are in the NH2-terminal region. (Orio )
The mouse beta3 subunit, excluding N-terminal splice variants, shares only 62.8% amino acid identity with its human counterpart. (Zheng )
Kcnmb3 : potassium large conductance calcium-activated channel, subfamily M beta member 3
The topology of alpha and beta subunits that make up BK channels can be seen in fig. 1 of Orio . The channel is formed by 4 alpha-subunits and probably 4 beta subunits. Regulatory beta subunits share a putative membrane topology, with two transmembrane segments connected by a 120- residue extracellular “loop” and with NH2 and COOH terminals oriented toward the cytoplasm (Fig. 1 ). The loop has three or four putative glycosylation sites. Four beta subunits have been cloned in mammals (Brenner , Knaus , Uebele , Xia ).
BKB3 was detected in testis, pancreas and spleen (Xia ).
There are four splice variants (BKB3a-d), whose differences are in the NH2-terminal region. Each splice variant confers different inactivation properties to the MaxiK channel. Whereas the BKB3a and BKB3c subunits confer similar inactivation properties, BKB3b induces a faster and incomplete inactivation process that becomes evi- dent only at large depolarizations (Xia ). It is unclear whether or not the BKB3d-subunit interacts with the alpha-subunit since coexpression of alpha- and BKB3d-subunits does not produce changes in the Ca2+ activation curves or in the gating kinetics of the MaxiK channel. (Orio )
The BKB3b auxiliary subunit, when coexpressed with the Slo alpha subunit, results in a particularly rapid (1ms), but incomplete inactivation, mediated by the cytosolic NH2 terminus of the BKB3b subunit (Xia et al., 2000 ). See Lingle  for by a two-step blocking mechanism of this process.