Article abstract
Nature Structural & Molecular Biology 15, 403 - 410 (2008)
Published online: 16 March 2008 | doi:10.1038/nsmb.1398
Reciprocal regulation of the Ca2+ and H+ sensitivity in the SLO1 BK channel conferred by the RCK1 domain
Shangwei Hou1, Rong Xu1, Stefan H Heinemann2 & Toshinori Hoshi1
Abstract
Increasing evidence suggests that intracellular H+ directly stimulates large-conductance Ca2+- and voltage-activated K+ (SLO1 BK) channels, thus providing a crucial link between membrane excitability and cell metabolism. Here we report that two histidine residues, His365 and His394, located in the intracellular regulator of conductance for K+ (RCK) 1 domain, serve as the H+ sensors of the SLO1 BK channel. Activation of the channel by H+ requires electrostatic interactions between the histidine residues and a nearby negatively charged residue involved in the channel's high-affinity Ca2+ sensitivity. Reciprocally, His365 and His394 also participate in the Ca2+-dependent activation of the channel, functioning as Ca2+ mimetics once they are protonated. Therefore, a common motif in the RCK1 domain mediates the stimulatory effects of both H+ and Ca2+, and provides a basis for the bidirectional coupling of cell metabolism and membrane electrical excitability.
- Department of Physiology, University of Pennsylvania, 3700 Hamilton Walk, Philadelphia, Pennsylvania 19104, USA.
- Center for Molecular Biomedicine, Department of Biophysics, Friedrich Schiller University Jena, Hans-Knöll-St. 2, D-07745 Jena, Germany.
Correspondence to: Toshinori Hoshi1 e-mail: hoshi@hoshi.org
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