Please use this identifier to cite or link to this item:
|Title:||C-terminal alternative splicing of CaV1.3 channels distinctively modulates their dihydropyridine sensitivity|
|Citation:||Huang, H., Yu, D., Soong, T.W. (2013-10). C-terminal alternative splicing of CaV1.3 channels distinctively modulates their dihydropyridine sensitivity. Molecular Pharmacology 84 (4) : 643-653. ScholarBank@NUS Repository. https://doi.org/10.1124/mol.113.087155|
|Abstract:||The transcripts of L-type voltage-gated calcium channels (CaV) 1.3 undergo extensive alternative splicing. Alternative splicing, particularly in the C terminus, drastically modifies gating properties of the channel. However, little is known about whether alternative splicing could modulate the pharmacologic properties of CaV1.3 in a manner similar to the paralogous CaV1.2. Here we undertook the screening of different channel splice isoforms harboring splice variations in either the IS6 segment or the C terminus. Unexpectedly, while inclusion of exon 8a or 8, which code for IS6, did not alter dihydropyridine (DHP) sensitivity, distinct pharmacologic properties were observed for the various C-terminal splice isoforms. In the presence of external Ca2+, fast inactivating splice variants including CaV1.342a and CaV1.343s with intact calmodulin-IQ domain interaction showed consistently low DHP sensitivity. Interestingly, attenuation of calcium-dependent inactivation with overexpression of calmodulin34 did not enhance the sensitivity of CaV1.342a, suggesting that the low DHP sensitivity may not be a result of fast channel inactivation. Alternatively, disruption of calmodulin-IQ domain binding in the CaV1.3Δ41 and full-length CaV1.342 channels was associated with heightened DHP sensitivity. In distinct contrast to the well-known modulation of DHP blockade of CaV1.2 channels, this study has therefore uncovered a novel mechanism for modulation of the pharmacologic properties of Ca V1.3 channels through posttranscriptional modification of the C terminus. Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics.|
|Source Title:||Molecular Pharmacology|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Jul 13, 2018
WEB OF SCIENCETM
checked on Jun 11, 2018
checked on May 11, 2018
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.