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- W4317639526 abstract "The calcium channel α 1A subunit gene codes for proteins with diverse structure and function. This diversity may be important for fine tuning neurotransmitter release at central and peripheral synapses. The α 1A C terminus, which serves a critical role in processing information from intracellular signaling molecules, is capable of undergoing extensive alternative splicing. The purpose of this study was to determine the extent to which C-terminal alternative splicing affects some of the fundamental biophysical properties of α 1A subunits. Specifically, the biophysical properties of two alternatively spliced α 1A subunits were compared. One variant was identical to an isoform identified previously in human brain, and the other was a novel isoform isolated from human spinal cord. The variants differed by two amino acids (NP) in the extracellular linker between transmembrane segments IVS3 and IVS4 and in two C-terminal regions encoded by exons 37 and 44. Expression in Xenopus oocytes demonstrated that the two variants were similar with respect to current–voltage relationships and the voltage dependence of steady-state activation and inactivation. However, the rates of activation, inactivation, deactivation, and recovery from inactivation were all significantly slower for the spinal cord variant. A chimeric strategy demonstrated that the inclusion of the sequence encoded by exon 44 specifically affects the rate of inactivation. These findings demonstrate that C-terminal structural changes alone can influence the way in which α 1A subunits respond to a depolarizing stimulus and add to the developing picture of the C terminus as a critical domain in the regulation of Ca 2+ channel function." @default.
- W4317639526 created "2023-01-21" @default.
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- W4317639526 date "2000-10-15" @default.
- W4317639526 modified "2023-10-18" @default.
- W4317639526 title "C-Terminal Alternative Splicing Changes the Gating Properties of a Human Spinal Cord Calcium Channel α1A Subunit" @default.
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- W4317639526 doi "https://doi.org/10.1523/jneurosci.20-20-07564.2000" @default.
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