Neuroscience 2000 Abstract
| Presentation Number: | 781.3 |
|---|---|
| Abstract Title: | Ca<SUP>2+</SUP>-dependent facilitation and inactivation of P/Q-type Ca<SUP>2+</SUP> channels: impact of an IQ-like CAM binding site on α<SUB>1A</SUB>. |
| Authors: |
DeMaria, C. D.*1
; Soong, T. W.3
; Alseikhan, B. A.1
; Alvania, R. S.1
; Agnew, W. S.2
; Yue, D. T.1
1Dept. of Biomed. Engr., Johns Hopkins Sch. Med., Baltimore, MD 2Dept. of Physiol., Johns Hopkins Sch. Med., Baltimore, MD 3Natl. Neurosci. Inst., Singapore, Singapore |
| 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 8:30 AM-8:45 AM |
| Location: | Room 283 |
| Keywords: | NEUROMODULATION, PRESYNAPTIC MECHANISMS, CALMODULIN, HEK CELLS |
Recombinant P/Q-type α1A) Ca2+ channels exhibit novel forms of Ca2+-dependent facilitation and inactivation (Lee et al, Nature 399:155), which may support short-term synaptic plasticity at central synapses (Borst et al, J Physiol, 513:149; Cuttle et al, ibid, 512:723). Both facilitation and inactivation reportedly involve calmodulin (CaM) binding to a CBD domain, situated on the distal α1A. carboxyl tail. By contrast, we recently found that Ca2+-dependent inactivation of L-type (α1C) Ca2+ channels relies on CaM binding to an IQ-like domain in the proximal carboxyl tail (Peterson et al, Neuron, 22:549), and an analogous motif on α1A (IQA) exhibits robust CaM binding. Here, we report that IQA is a critical structural determinant of both facilitation and inactivation in P/Q channels. Facilitation of wildtype P/Q channels (α1A β2a α2δ) is apparent during prepulse protocols with Ca2+ as charge carrier (A, middle row), where test-pulse currents without a prepulse (gray) slowly increased with maintained Ca2+ entry (facilitation), while test-pulse currents following a prepulse (black)were already facilitiated by prepulse entry. Ca2+- dependent inactivation is manifest during long test pluses (B, middle row) by the enhanced decay of Ca2+ (gray) vs. Ba2+ (black) currents. By contrast, alanine-scanning mutation of IQA produced a pronounced knockout of facilitation (A, bottom row), as well as enhanced inactivation without Ca2+ dependence (B, bottom row). These results heighten expectations that the IQ-like motif supports multiple regulatory functions across the family of Ca2+ channels. RO1NS37115, F32 MH12767, NMRC Singapore.
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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