Unified mechanisms of Ca2+ regulation across the Ca2+ channel family.
L-type (CaV1.2) and P/Q-type (CaV2.1) calcium channels possess lobe-specific CaM regulation, where Ca2+ binding to one or the other lobe of CaM triggers regulation, even with inverted polarity of modulation between channels. Other major members of the CaV1-2 channel family, R-type (CaV2.3) and N-type (CaV2.2), have appeared to lack such CaM regulation. We report here that R- and N-type channels undergo Ca(2+)-dependent inactivation, which is mediated by the CaM N-terminal lobe and present only with mild Ca2+ buffering (0.5 mM EGTA) characteristic of many neurons. These features, together with the CaM regulatory profiles of L- and P/Q-type channels, are consistent with a simplifying principle for CaM signal detection in CaV1-2 channels-independent of channel context, the N- and C-terminal lobes of CaM appear invariably specialized for decoding local versus global Ca2+ activity, respectively.
Liang
Haoya
H
Ca2+ Signals Laboratory, Departments of Biomedical Engineering and Neuroscience, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA.
DeMaria
Carla D
CD
Erickson
Michael G
MG
Mori
Masayuki X
MX
Alseikhan
Badr A
BA
Yue
David T
DT
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020864:Calcium Channels, N-Type / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020865:Calcium Channels, P-Type / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020907:Calcium Channels, Q-Type / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020908:Calcium Channels, R-Type / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism*; D002417:Cattle; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008969:Molecular Sequence Data; D051381:Rats; D017386:Sequence Homology, Amino Acid
D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D020908:Calcium Channels, R-Type; D002147:Calmodulin; D002118:Calcium