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Title: Alternative splicing as a molecular switch for Ca2+/calmodulin- dependent facilitation of P/Q-type Ca2+ channels
Authors: Chaudhuri, D.
Chang, S.-Y.
DeMaria, C.D.
Alvania, R.S.
Soong, T.W. 
Yue, D.T.
Keywords: Ca 2+-dependent inactivation
Developmental alternative splicing
EF hand
Exon 37
Short-term synaptic plasticity
Issue Date: 14-Jul-2004
Citation: Chaudhuri, D., Chang, S.-Y., DeMaria, C.D., Alvania, R.S., Soong, T.W., Yue, D.T. (2004-07-14). Alternative splicing as a molecular switch for Ca2+/calmodulin- dependent facilitation of P/Q-type Ca2+ channels. Journal of Neuroscience 24 (28) : 6334-6342. ScholarBank@NUS Repository.
Abstract: Alternative splicing of the P/Q-type channel (Cav2.1) promises customization of the computational repertoire of neurons. Here we report that concerted splicing of its main α1A subunit, at both an EF-hand-like domain and the channel C terminus, controls the form of Ca 2+-dependent facilitation (CDF), an activity-dependent enhancement of channel opening that is triggered by calmodulin. In recombinant channels, such alternative splicing switches CDF among three modes: (1) completely "ON" and driven by local Ca2+ influx through individual channels, (2) completely "OFF," and (3) partially OFF but inducible by elevated global Ca2+ influx. Conversion from modes 1 to 3 represents an unprecedented dimension of control. The physiological function of these variants is likely important, because we find that the distribution of EF-hand splice variants is strikingly heterogeneous in the human brain, varying both across regions and during development.
Source Title: Journal of Neuroscience
ISSN: 02706474
Appears in Collections:Staff Publications

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