Logged in as a Visitor.
potassium large conductance calcium-activated channel, subfamily M, beta member 4
Beta-Subunits alter the Ca2+ sensitivity and gating kinetics of MaxiK channels, greatly contributing to MaxiK channel diversity. They also modify the MaxiK channel pharmacological properties, changing toxin binding and acting as receptors for drugs. Thus they allow the MaxiK channel to play important physiological roles. Orio 
MaxiK (BK) channels can be formed by 2 subunits: the pore-forming alpha subunit and the modulatory beta subunit. The protein encoded by the gene KCNMB4 is BKB4, an auxiliary beta subunit which slows activation kinetics, leads to steeper calcium sensitivity, and shifts the voltage range of current activation to more negative potentials than does the beta 1 subunit.
Sequence similarities are major between BKB1-BKB2 and BKB2-BKB3, respectively. BKB4 is the most distantly related of all b-subunits. b-Subunit orthologs have not been described in Drosophila or in the worm C. elegans, suggesting that this protein is a “novel” acquisition in evolution. Orio 
Kcnmb4 : potassium large conductance calcium-activated channel, subfamily M, beta member 4
The BKB4-subunit decreases the CTX binding strength. If the external loops of the BKB1- and BKB4-subunits are exchanged (chimeras b1Lb4 and b4Lb1), the phenotypes obtained regarding toxin binding correspond to their respective loops (e.g., chimera b1Lb4 has a toxin sensitivity corresponding to the BKB4 subunit). These results suggest that the loops of the b-subunits determine the characteristic of toxin binding. (Meera , Orio )
BKB4 channels were not blocked by 100 nM charybdotoxin or iberiotoxin, and were activated by 17-beta-estradiol. Behrens 
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 in Orio ). The loop has three or four putative glycosylation sites (Orio ). At present, four beta-subunits have been cloned in mammals (Meera , Brenner , Knaus (#a1187), Uebele , Xia ). Because CTX is a pore-blocking toxin, it is suggested that the extracellular loop of b-subunits (at least BKB1 and BKB4) faces the pore and is very close to it (Meera ).
The BKB4-subunit, also cloned from human EST databases, is expressed mainly in brain. Orio 
Coexpression of BKB4 with the alpha-subunit decreases the apparent Ca2+ sensitivity of the MaxiK channel (Brenner , Meera ). Although this subunit slows down channel activation kinetics in a manner similar to the b1-subunit, the deactivation kinetics is very fast (similar to that observed in absence of the b-subunit; see Fig. 2 in Orio  and Brenner ). These results indicate that the functional coupling of this subunit with the alpha-subunit is different from that induced by the other b-subunits.