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Calmodulin Is the Ca2+ Sensor for Ca2+-Dependent Inactivation of L-Type Calcium Channels
Open accessAbstract
Elevated intracellular Ca2+ triggers inactivation of L-type calcium channels, providing negative Ca2+ feedback in many cells. Ca2+ binding to the main alpha1c 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 alpha1c. 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.
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Cited by
Structure and Regulation of Voltage-Gated Ca 2+ Channels
Catterall, W. A. (2000) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.16.1.521 · Cited by 2,344
Voltage-Gated Calcium Channels
Catterall, W. A. (2011) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a003947 · Cited by 1,628
O'Hara, T., Virág, L., Varró, A., & Rudy, Y. (2011) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002061 · Cited by 1,196
Dolmetsch, R. E., Pajvani, U., Fife, K., Spotts, J. M., & Greenberg, M. E. (2001) · Science · doi:10.1126/science.1063395 · Cited by 900
Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men
Rorsman, P., & Ashcroft, F. M. (2018) · Physiological Reviews · doi:10.1152/physrev.00008.2017 · Cited by 793
Metadata
- Authors
- Peterson, B. Z., DeMaria, C. D., & Yue, D. T.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 1999-03
- Volume
- 22
- Issue
- 3
- Pages
- 549-558
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2087062865
- Cited by
- 856
- References
- 0
- FWCI
- 15.99
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- CoChat. (2026). Citation check: Calmodulin Is the Ca2+ Sensor for Ca2+-Dependent Inactivation of L-Type Calcium Channels. https://app.cochat.ai/papers/10.1016/s0896-6273(00)80709-6
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- Peterson, B. Z., DeMaria, C. D., & Yue, D. T. (1999). Calmodulin Is the Ca2+ Sensor for Ca2+-Dependent Inactivation of L-Type Calcium Channels. Neuron. https://doi.org/10.1016/s0896-6273(00)80709-6
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