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A structural motif in the C-terminal tail of slo1 confers carbon monoxide sensitivity to human BK_Ca channels

Lookup NU author(s): Dr Seva TelezhkinORCiD

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Abstract

Carbon monoxide (CO) is a potent activator of large conductance, calcium-dependent potassium (BK_Ca) channels of vascular myocytes and carotid body glomus cells or when heterologously expressed. Using the human BK_Ca channel α₁-subunit (hSlo1; KCNMA1) stably and transiently expressed in human embryonic kidney 293 cells, the mechanism and structural basis of channel activation by CO was investigated in inside–out, excised membrane patches. Activation by CO was concentration dependent (EC₅₀ ∼20 μM), rapid, reversible, and evoked a shift in the V_0.5 of −20 mV. CO evoked no changes in either single channel conductance or in deactivation rate but augmented channel activation rate. Activation was independent of the redox state of the channel, or associated compounds/protein partners, and was partially dependent on [Ca²⁺]_i in the physiological range (100–1,000 nM). Importantly, CO “super-stimulated” BK_Ca activity even in saturating [Ca²⁺]_i. Single or double mutation of two histidine residues previously implicated in CO sensing did not suppress CO activation but replacing the S9–S10 module of the C-terminal of Slo1 with that of Slo3 completely prevented the action of CO. These findings show that a motif in the S9–S10 part of the C-terminal is essential for CO activation and suggest that this gas transmitter activates the BK_Ca channel by redox-independent changes in gating.

Publication metadata

Author(s): Williams SE, Brazier SP, Baban N, Telezhkin V, Müller CT, Riccardi D, Kemp PJ

Publication type: Article

Publication status: Published

Journal: Pflügers Archiv - European Journal of Physiology

Year: 2008

Volume: 456

Issue: 3

Pages: 561-572

Print publication date: 01/06/2008

Online publication date: 05/01/2008

ISSN (print): 0031-6768

Publisher: Springer

URL: https://doi.org/10.1007/s00424-007-0439-4

DOI: 10.1007/s00424-007-0439-4

PubMed id: 18180950

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