Journal
FRONTIERS IN PHYSIOLOGY
Volume 5, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fphys.2014.00383
Keywords
BK channel; Slo1; KCNMB; BK beta subunits; BK pharmacology; auxiliary subunits
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Funding
- FONDECYT [1110430]
- Millennium Scientific Initiative of the Chilean Ministry of Economy, Development and Tourism
- Pontificia Universidad Javeriana [ID5571]
- COLCIENCIAS doctoral fellowships
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Coded by a single gene (Slo1, KCM) and activated by depolarizing potentials and by a rise in intracellular Ca2+ concentration, the large conductance voltage- and Ca2+-activated K+ channel (BK) is unique among the superfamily of K+ channels. BK channels are tetramers characterized by a pore-forming a subunit containing seven transmembrane segments (instead of the six found in voltage-dependent K+ channels) and a large C terminus composed of two regulators of K+ conductance domains (RCK domains), where the Ca2+-binding sites reside. BK channels can be associated with accessory (beta subunits and, although different BK modulatory mechanisms have been described, greater interest has recently been placed on the role that the (3 subunits may play in the modulation of BK channel gating due to its physiological importance. Four beta subunits have currently been identified (i.e., beta 1, beta 2, beta 3, and beta 4) and despite the fact that they all share the same topology, it has been shown that every beta subunit has a specific tissue distribution and that they modify channel kinetics as well as their pharmacological properties and the apparent Ca2+ sensitivity of the a subunit in different ways. Additionally, different studies have shown that natural, endogenous, and synthetic compounds can modulate BK channels through beta subunits. Considering the importance of these channels in different pathological conditions, such as hypertension and neurological disorders, this review focuses on the mechanisms by which these compounds modulate the biophysical properties of BK channels through the regulation of beta subunits, as well as their potential therapeutic uses for diseases such as those mentioned above.
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