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(Circulation Research. 2000;87:537.)
© 2000 American Heart Association, Inc.

Reports

Splice Variants Reveal the Region Involved in Oxygen Sensing by Recombinant Human L-Type Ca²⁺ Channels

Ian M. Fearon, Gyula Varadi, Sheryl Koch, Idit Isaacsohn, Stephen G. Ball, Chris Peers

From the Institute for Cardiovascular Research (I.M.F., S.G.B., C.P.), The University of Leeds, Leeds, UK; Institute of Molecular Pharmacology and Biophysics (I.I., S.K., G.V.), University of Cincinnati College of Medicine, Cincinnati, Ohio.

Correspondence to Dr Ian Fearon, Institute for Cardiovascular Research, The University of Leeds, Leeds LS2 9JT, UK. E-mail cvsimf{at}leeds.ac.uk

Regulation of vascular smooth muscle Ca²⁺ channels by oxygen tension contributes importantly to hypoxic vasodilatation. We previously described the inhibitory effects of hypoxia on the recombinant human cardiac L-type Ca²⁺ channel _1C subunit (hHT isoform) expressed in HEK 293 cells. We now demonstrate that hypoxia inhibits only one of the three naturally occurring splice variants of this channel that differ only in the C-terminal domain, permitting identification of a 71-amino acid insert in the C-terminal region of the channel that confers oxygen sensitivity. Selective restriction of the spliced insert allowed determination of a 39-amino acid region essential for oxygen sensing. This represents the first identification of the structural region of an ion channel required for sensing changes in oxygen tension.

Key Words: L-type Ca²⁺ channel • _1C subunit • hypoxia • inhibition

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