Hypoxia inhibits the recombinant alpha 1C subunit of the human cardiac L-type Ca2+ channel.
1. Whole-cell patch clamp recordings were used to investigate the effects of hypoxia on recombinant human L-type Ca2+ channel alpha 1C subunits stably expressed in human embryonic kidney (HEK 293) cells. 2. Ca2+ channel currents were reversibly inhibited by hypoxia (PO2 < 90 mmHg). The degree of inhibition depended on the charge carrier used, Ca2+ currents being more O2 sensitive than Ba2+ currents. 3. Hypoxic inhibition of Ca2+ channel currents was more pronounced at lower activating membrane potentials (< or = +30 mV), and was associated with a slowing of activation kinetics. Current inactivation and deactivation were unaffected by hypoxia. 4. Since hypoxia similarly regulates native L-type Ca2+ channels in vascular smooth muscle cells, our results suggest that hypoxic regulation of L-type Ca2+ channels arises from modification of structural features of the alpha 1 subunit common to cardiac and smooth muscle L-type channels.
Fearon
I M
IM
Institute for Cardiovascular Research, University of Leeds, UK.
Palmer
A C
AC
Balmforth
A J
AJ
Ball
S G
SG
Mikala
G
G
Schwartz
A
A
Peers
C
C
D000818:Animals; D001464:Barium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D002478:Cells, Cultured; D004594:Electrophysiology; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D007700:Kinetics; D008564:Membrane Potentials / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D016366:Open Reading Frames; D018408:Patch-Clamp Techniques; D011994:Recombinant Proteins / Q000378:metabolism; D014982:Xenopus laevis
D015220:Calcium Channels; D011994:Recombinant Proteins; D001464:Barium