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

  • Sandile E. Williams
  • Stephen P. Brazier
  • Nian Baban
  • Vsevolod Telezhkin
  • Carsten T. Müller
  • Daniela Riccardi
  • Paul J. KempEmail author
Ion Channels

Abstract

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.

Keywords

Potassium channel Heme Hemeoxygenase Carbon monoxide Gas transmitter 

Notes

Acknowledgments

Funded by the British Heart Foundation Programme Grant RG/03/001.

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Sandile E. Williams
    • 1
  • Stephen P. Brazier
    • 1
  • Nian Baban
    • 1
  • Vsevolod Telezhkin
    • 1
  • Carsten T. Müller
    • 1
  • Daniela Riccardi
    • 1
  • Paul J. Kemp
    • 1
    Email author
  1. 1.School of BiosciencesCardiff UniversityCardiffUK

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