Neuroscience 2000 Abstract
| Presentation Number: | 781.4 |
|---|---|
| Abstract Title: | Systematic determination of splice variation in human P/Q-type Ca<SUP>2+</SUP> channels: functional impact of C-terminal variants. |
| Authors: |
Soong, T. W.*1
; DeMaria, C. D.2
; Mittman, S.3
; Agnew, W. S.3
; Yue, D. T.2
1Natl. Neurosci. Inst., Jalan Tan Tock Seng, Singapore 2Dept. of Biomed. Engr., Johns Hopkins Sch. Med., Baltimore, MD 3Dept. of Physiology, Johns Hopkins Sch. Med., Baltimore, MD |
| Primary Theme and Topics |
C. Excitable Membranes and Synaptic Transmission - 36. Calcium channels |
| Secondary Theme and Topics | C. Excitable Membranes and Synaptic Transmission<br />- 30. Presynaptic mechanisms |
| Session: |
781. Calcium channels Slide |
| Presentation Time: | Thursday, November 9, 2000 8:45 AM-9:00 AM |
| Location: | Room 283 |
| Keywords: | Neurotransmission, Neuromodulation, Presynaptic Mechanisms, Structural Diversity |
Alternative splicing of the human P/Q-type (α1A) channel provides a potentially rich source of functional diversity. Here, exon scanning of the human α1A gene revealed the presence of 9 loci in which the alternative use of junctional splice sites or exons produces different splice variants. Four alternative splice sites in the carboxyl tail, at exons 37, 43, 44 and 47, are particularly intriguing, because of their proximity to a reputed calmodulin binding domain (CBD) in exon 42 (Lee et al, Nature 399:155), which may support Ca2+-dependent inactivation and facilitation of P/Q-type channels. Interestingly, all permutations of the presence or absence of adjacent exons 43/44 (++, +-, -+, and --) were detected in human cerebellar cDNAs. We therefore investigated the functional impact of alternative splicing at exons 43 and 44, using whole-cell analysis of recombinant channels expressed in HEK 293 cells. While all combinations showed facilitation, splice variation produced subtle differences in the strength of Ca2+-dependent inactivation, as gauged by the enhanced decay of Ca2+ vs. Ba2+ currents during 300-ms depolarizations (A, traces normalized to facilitate kinetic comparison). Exemplar -- currents (A, top) illustrate the typical level of Ca2+ inactivation observed with most combinations, while +- currents (A, bottom) were notable for their unusually weak Ca2+-dependent inactivation. Population data (B), showing the fraction of remaining current at the end of 300-ms depolarizations (Γ300), confirmed these trends. These results point to splice variation as a potential mechanism to fine tune the activity-dependent performance of P/Q-type channels in vivo. NMRC Singapore, RO1 NS37115.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2000 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2000. Online.
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