Abstract
The passage of Ca2+ ions through voltage-gated Ca2+ channels triggers a wide range of signaling pathways but also fundamentally regulates further Ca2+ influx through these channels. Cav1.2 (L-type) and Cav2.1 (P/Q-type) channels undergo a dual feedback regulation by Ca2+, which is manifested as enhanced facilitation and inactivation of Ca2+ currents compared to Ba2+ currents. Ca2+-dependent facilitation and inactivation are distinct biophysical processes but are linked through a common molecular mechanism. The ubiquitous Ca2+-sensing protein calmodulin binds directly to multiple sequences in the Ca2+ channel α1 subunit, causing Ca2+-dependent conformational changes that favor facilitated or inactivated states of the channel. In the nervous system, Ca2+ binding proteins related to CaM also contribute to modulation of Ca2+ channels, which may diversify Ca2+ signaling in different neurons. In all excitable cells, Ca2+-dependent facilitation and inactivation of voltage-gated Ca2+ channels may be a general mechanism for fine-tuning Ca2+ entry to protect against toxic Ca2+ overloads and to control the specificity with which Ca2+-dependent signaling pathways are activated.
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Lee, A., Catterall, W.A. (2005). Ca2+-Dependent Modulation of Voltage-Gated Ca2+ Channels. In: Voltage-Gated Calcium Channels. Molecular Biology Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/0-387-27526-6_11
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DOI: https://doi.org/10.1007/0-387-27526-6_11
Publisher Name: Springer, Boston, MA
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