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

Williams, S. E., Brazier, Stephen Paul, Baban, Nian, Telezhkin, Vsevolod ORCID:, Muller, Carsten Theodor ORCID:, Riccardi, Daniela ORCID: and Kemp, Paul J ORCID: 2008. A structural motif in the C-terminal tail of slo1 confers carbon monoxide sensitivity to human BKCa channels. Pflugers Archiv-European Journal of Physiology 456 (3) , pp. 561-572. 10.1007/s00424-007-0439-4

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Carbon monoxide (CO) is a potent activator of large conductance, calcium-dependent potassium (BKCa) channels of vascular myocytes and carotid body glomus cells or when heterologously expressed. Using the human BKCa 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 V0.5 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” BKCa 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 BKCa channel by redox-independent changes in gating.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Subjects: Q Science > QP Physiology
Uncontrolled Keywords: Potassium channel; Heme; Hemeoxygenase; Carbon monoxide; Gas transmitter
Publisher: Springer Verlag
ISSN: 0031-6768
Last Modified: 18 Oct 2022 12:18

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