Maxi-K_Ca, a Unique Member of the Voltage-Gated K Channel Superfamily

Abstract

Large-conductance, voltage-, and Ca(2+)-sensitive K(+) (maxi-K(Ca)) channels regulate neuronal and smooth muscle excitability. Their pore-forming alpha-subunit shows similarities with voltage-gated channels and indeed can open in the practical absence of Ca(2+). The NH(2) terminus is unique, with a seventh transmembrane segment involved in beta-subunit modulation. The long COOH terminus is implied in Ca(2+) modulation.

Leucine Zipper Domain Targets cAMP-dependent Protein Kinase to Mammalian BK Channels

“…In these assays we stimulated PKA activity intimately associated with the channel by applying cAMP to the intracellular face of isolated inside-out patches. As previously reported (17) the effects of cAMP in this system are dependent upon the presence of Mg-ATP, and the actions of cAMP are completely abolished by the PKA inhibitor peptide PKI [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] . Although STREX channels are inhibited whereas ZERO channels are activated by PKA closely associated with the channel (17), the short LZ1-competing peptides effectively blocked PKAdependent regulation of either splice variant.…”

“…BK channels play a central role in the regulation of cellular excitability because they are activated directly by both voltage and intracellular free calcium (4 -6) and potently modulated by reversible protein phosphorylation (1). For example, they provide a dynamic link between electrical and chemical signaling events in cells, are major determinants of vascular smooth muscle tone (5,7), and regulate action potential duration and frequency as well as neurotransmitter and hormone release in neurons and endocrine cells (6,8). A single gene (KCNMA1) encodes for the pore-forming ␣-subunits of BK channels in all mammalian tissues (9).…”

Large conductance Ca2+-activated K+ (BK) channel: Activation by Ca2+ and voltage

“…Like Kv channels, the BK channel is a tetramer (Shen et al, 1994); unlike Kv channels, however, the BK channel protein consists of seven transmembrane domains (S0-S6) that lead to an exoplasmic N-terminus (Fig. 1;Meera et al, 1997;Wallner et al, 1996;Toro et al, 1998). The large C-terminus (containing about twice as many amino acids as S0-S6) has four hydrophobic domains (S7-S10), and Salkoff's group identified two molecular domains (S0-S8, "core" and S9-S10, "tail") that, when expressed together, were able to produce functional channels (Wei et al, 1994 A. D362/D367, M513 and the calcium bowl define sites that when mutated decrease the highaffinity Ca 2+ sensitivity of the BK channel.…”

The Cytoplasmic Tail of Large Conductance, Voltage- and Ca2+-activated K+ (MaxiK) Channel Is Necessary for Its Cell Surface Expression

“…A single gene encodes the ␣-subunit with the S1-S6 region homologous to the tetrameric voltage-gated K ϩ channels, especially in the poreforming domain, S5-P-S6, and the voltage-sensing element, S4 (21,22). Structures unique to the MaxiK channel ␣-subunit include an additional N-terminal transmembrane domain, S0, and a large C terminus.…”

“…The interaction of the MaxiK ␣-subunit with the modulatory ␤-subunits or other accessory proteins partially explains their overall functional diversity. More importantly, the function variation of MaxiK channels comes from the alternative splicing of its ␣-subunit (17,22,32). So far, ten splice sites have been reported with most of them localized in the intracellular C terminus.…”