MaxiK channel partners: physiological impact.
The basic functional unit of the large-conductance, voltage- and Ca2+-activated K+ (MaxiK, BK, BKCa) channel is a tetramer of the pore-forming alpha-subunit (MaxiKalpha) encoded by a single gene, Slo, holding multiple alternative exons. Depending on the tissue, MaxiKalpha can associate with modulatory beta-subunits (beta1-beta4) increasing its functional diversity. As MaxiK senses and regulates membrane voltage and intracellular Ca2+, it links cell excitability with cell signalling and metabolism. Thus, MaxiK is a key regulator of vital body functions, like blood flow, uresis, immunity and neurotransmission. Epilepsy with paroxysmal dyskinesia syndrome has been recognized as a MaxiKalpha-related disorder caused by a gain-of-function C-terminus mutation. This channel region is also emerging as a key recognition module containing sequences for MaxiKalpha interaction with its surrounding signalling partners, and its targeting to cell-specific microdomains. The growing list of interacting proteins highlights the possibility that associations with the C-terminus of MaxiKalpha are dynamic and depending on each cellular environment. We speculate that the molecular multiplicity of the C-terminus (and intracellular loops) dictated by alternative exons may modulate or create additional interacting sites in a tissue-specific manner. A challenge is the dissection of MaxiK macromolecular signalling complexes in different tissues and their temporal association/dissociation according to the stimulus.
Lu
Rong
R
Dept. Anesthesiology, UCLA, BH-509A CHS, Box 957115, Los Angeles, CA 90095-7115, USA. ltoro@ucla.edu.
Alioua
Abderrahmane
A
Kumar
Yogesh
Y
Eghbali
Mansoureh
M
Stefani
Enrico
E
Toro
Ligia
L
D000818:Animals; D020013:Calcium Signaling / Q000502:physiology; D051242:Caveolin 1 / Q000378:metabolism; D004827:Epilepsy / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000378:metabolism; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000235:genetics; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits / Q000378:metabolism*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D008564:Membrane Potentials / Q000502:physiology; D009130:Muscle, Smooth / Q000378:metabolism; D009154:Mutation; D011494:Protein Kinases / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism
D051242:Caveolin 1; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; D018343:Receptors, Adrenergic, beta-2; D011494:Protein Kinases