Calmodulin is the Ca2+ sensor for Ca2+-dependent inactivation of L- type calcium channels

Blaise Z. Peterson, Carla D. DeMaria, David T. Yue

Research output: Contribution to journalArticle

652 Citations (Scopus)

Abstract

Elevated intracellular Ca2+ triggers inactivation of L-type calcium channels, providing negative Ca2+ feedback in many cells. Ca2+ binding to the main α(1C) channel subunit has been widely proposed to initiate such Ca2+-dependent inactivation. Here, we find that overexpression of mutant, Ca2+-insensitive calmodulin (CAM) ablates Ca2+-dependent inactivation in a 'dominant-negative' manner. This result demonstrates that CaM is the actual Ca2+ sensor for inactivation and suggests that CaM is constitutively tethered to the channel complex. Inactivation is likely to occur via Ca2+- dependent interaction of tethered CaM with an IQ-like motif on the carboxyl tail of α(1C). CaM also binds to analogous IQ regions of N-, P/Q-, and R- type calcium channels, suggesting that CaM-mediated effects may be widespread in the calcium channel family.

Original languageEnglish (US)
Pages (from-to)549-558
Number of pages10
JournalNeuron
Volume22
Issue number3
DOIs
StatePublished - Mar 1999

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R-Type Calcium Channels
Q-Type Calcium Channels
L-Type Calcium Channels
Calmodulin
Calcium Channels

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Peterson, Blaise Z. ; DeMaria, Carla D. ; Yue, David T. / Calmodulin is the Ca2+ sensor for Ca2+-dependent inactivation of L- type calcium channels. In: Neuron. 1999 ; Vol. 22, No. 3. pp. 549-558.
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Calmodulin is the Ca2+ sensor for Ca2+-dependent inactivation of L- type calcium channels. / Peterson, Blaise Z.; DeMaria, Carla D.; Yue, David T.

In: Neuron, Vol. 22, No. 3, 03.1999, p. 549-558.

Research output: Contribution to journalArticle

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