Abstract
L-type (Ca V1.2) and P/Q-type (Ca V2.1) calcium channels possess lobe-specific CaM regulation, where Ca 2+ binding to one or the other lobe of CaM triggers regulation, even with inverted polarity of modulation between channels. Other major members of the Ca V1-2 channel family, R-type (Ca V2.3) and N-type (Ca V2.2), 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 Ca 2+ 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 Ca V1-2 channels—independent of channel context, the N- and C-terminal lobes of CaM appear invariably specialized for decoding local versus global Ca 2+ activity, respectively.
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