Transfer of beta subunit regulation from high to low voltage-gated Ca2+ channels.
High voltage-activated Ca(2+) channel expression and gating is controlled by their beta subunits. Although the sites of interaction are known at the atomic level, how beta modulates gating remains to be determined. Using a chimeric approach, beta subunit regulation was conferred to a low voltage-activated channel. Regulation was dependent on a rigid linker connecting the alpha(1) interaction domain to IS6. Chimeric channels also revealed a role for IS6 in channel gating. Taken together, these results support a direct coupling model where beta subunits alter movements in IS6 that occur as the channel transits between closed, open, and inactivated states.
Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA.
Juan Manuel
JM
Arias
Janet
J
Murbartián
Iuliia
I
Vitko
Jung-Ha
JH
Lee
Edward
E
Perez-Reyes
D000595:Amino Acid Sequence; D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000737:chemistry / Q000378:metabolism*; D020864:Calcium Channels, N-Type / Q000276:immunology; D020747:Calcium Channels, T-Type / Q000276:immunology; D002460:Cell Line; D002942:Circular Dichroism; D004594:Electrophysiology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
D015220:Calcium Channels; D020864:Calcium Channels, N-Type; D020747:Calcium Channels, T-Type; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D002118:Calcium