TY - JOUR
T1 - Unified mechanisms of Ca2+ regulation across the Ca 2+ channel family
AU - Liang, Haoya
AU - DeMaria, Carla D.
AU - Erickson, Michael G.
AU - Mori, Masayuki X.
AU - Alseikhan, Badr A.
AU - Yue, David T.
N1 - Funding Information:
We thank Tracy Morrison for collaborating on the first experiments detecting N-type channel CDI; and Terry Snutch (α 1E ) and SIBIA/Merck (α 1B ) for the generous gift of clones. This work was supported by an NIH NRSA fellowship (C.D.D.) and grants from the NIH (D.T.Y.).
PY - 2003/9/11
Y1 - 2003/9/11
N2 - 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 Ca2+-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.
AB - 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 Ca2+-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.
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U2 - 10.1016/S0896-6273(03)00560-9
DO - 10.1016/S0896-6273(03)00560-9
M3 - Article
C2 - 12971895
AN - SCOPUS:0141518276
SN - 0896-6273
VL - 39
SP - 951
EP - 960
JO - Neuron
JF - Neuron
IS - 6
ER -