MaxiK channels and smooth muscle partners

University of Oxford (2005) J Physiol 568P, SA17

Research Symposium: MaxiK channels and smooth muscle partners

Toro, Ligia; Alioua, Abderrahmane; Lu, Rong; Kumar, Yogesh; Eghbali, Mansoureh; Stefani, Enrico;

1. Department of Anesthesiology, UCLA, Los Angeles, CA, USA.

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Ca2 -activated, voltage-dependent K channels also called MaxiK or BKCa because of their large conductance are abundant proteins in all smooth muscles. MaxiK channels are key regulators of vascular tone acting as a rheostat that fine tunes the membrane potential and intracellular Ca2 concentration. In smooth muscle, they are formed by the coassembly of four α subunits that form the channel pore with four regulatory β1 subunits. β1 subunits profoundly modify how the channel responds to Ca2 , voltage, intracellular signalling and pharmacological agents. The α subunit is the product of a single gene but the potential to express plenty of splice variant isoforms. The β1 subunit belongs to a family of genes that are largely tissue specific, β1 being the smooth muscle archetype. MaxiK channels are targets of vasoactive substances including vasorelaxants (e.g. nitric oxide-, arachidonic acid-pathways), and vasoconstrictors (e.g. angiotensin II, 5-hydroxytryptamine, phenylephrine, thromboxane A2). A newly discovered pathway for vasoconstriction links constricting agonist stimulation to c-Src tyrosine kinase activation followed by phosphorylation and inhibition of MaxiK channel activity (Alioua et al. 2002), which would result in membrane depolarization, Ca2 entry and contraction. Besides the β1 subunit, MaxiK channels receive the aid of associated partner proteins that help in their function and to localize them in specific microdomains. Recent evidence indicates that at least a fraction of MaxiK channels are localized in caveolae structures and may interact with caveolin-1 in human myometrium (Brainard et al. 2005). Both MaxiK and caveolin-1 are important for vascular function as disruption of caveolae with β-methylcyclodextrine impairs agonist-induced vascular contraction and MaxiK α and β1 subunit gene ablation produces smooth muscle related disabilities (Brenner et al. 2000; Meredith et al. 2004). Thus, it is predicted that MaxiK channel forms functional units with receptors, tyrosine kinases and caveolin-1 in specialized microdomains.



Where applicable, experiments conform with Society ethical requirements.

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