Unified mechanisms of Ca2+ regulation across the Ca2+ channel family

Haoya Liang; Carla D DeMaria; Michael G Erickson; Masayuki X Mori; Badr A Alseikhan; David T Yue

doi:10.1016/s0896-6273(03)00560-9

Unified mechanisms of Ca2+ regulation across the Ca2+ channel family

Neuron. 2003 Sep 11;39(6):951-60. doi: 10.1016/s0896-6273(03)00560-9.

Authors

Haoya Liang¹, Carla D DeMaria, Michael G Erickson, Masayuki X Mori, Badr A Alseikhan, David T Yue

Affiliation

¹ Ca2+ Signals Laboratory, Departments of Biomedical Engineering and Neuroscience, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA.

PMID: 12971895
DOI: 10.1016/s0896-6273(03)00560-9

Abstract

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.

Publication types

Research Support, U.S. Gov't, P.H.S.

MeSH terms

Amino Acid Sequence
Animals
Calcium / metabolism*
Calcium Channels / chemistry
Calcium Channels / genetics*
Calcium Channels / metabolism*
Calcium Channels, L-Type / chemistry
Calcium Channels, L-Type / genetics
Calcium Channels, L-Type / metabolism
Calcium Channels, N-Type / chemistry
Calcium Channels, N-Type / genetics
Calcium Channels, N-Type / metabolism
Calcium Channels, P-Type / chemistry
Calcium Channels, P-Type / genetics
Calcium Channels, P-Type / metabolism
Calcium Channels, Q-Type / chemistry
Calcium Channels, Q-Type / genetics
Calcium Channels, Q-Type / metabolism
Calcium Channels, R-Type / chemistry
Calcium Channels, R-Type / genetics
Calcium Channels, R-Type / metabolism
Calmodulin / metabolism*
Cattle
Cell Line
Dose-Response Relationship, Drug
Humans
Molecular Sequence Data
Rats
Sequence Homology, Amino Acid

Substances

Calcium Channels
Calcium Channels, L-Type
Calcium Channels, N-Type
Calcium Channels, P-Type
Calcium Channels, Q-Type
Calcium Channels, R-Type
Calmodulin
Calcium