Neuroscience 2001 Abstract
| Presentation Number: | 14.2 |
|---|---|
| Abstract Title: | Inhibition of Ca<sub>v</sub>2.1 Ca<sup>2+</sup> channels by a neuronal Ca<sup>2+</sup> binding protein. |
| Authors: |
Lee, A.*1
; Westenbroek, R. E.1
; Haeseleer, F.2
; Palczewski, K.1,2
; Scheuer, T.1
; Catterall, W. A.1
1Pharmacology, University of Washington, Seattle, WA 2Opthalmology, University of Washington, Seattle, WA |
| Primary Theme and Topics |
Synaptic Transmission and Excitability - Voltage-Dependent Ion Channels -- Calcium channels |
| Session: |
14. Voltage-dependent ion channels: calcium channels Slide |
| Presentation Time: | Sunday, November 11, 2001 8:15 AM-8:30 AM |
| Location: | Room 32B |
| Keywords: | CALCIUM CHANNEL, CALMODULIN, PRESYNAPTIC, NEURON |
Ca2+-dependent inactivation and facilitation of presynaptic Cav2.1 Ca2+ channels can produce corresponding changes in synaptic efficacy. We have shown that this dual-feedback regulation of Cav2.1 by Ca2+ is mediated by calmodulin (CaM) through a direct interaction with a CaM-binding domain (CBD) in the α1 subunit of Cav2.1 (α12.1). Ca2+-binding protein 1 (CaBP1) is a neuron-specific isoform of CaM-like proteins that could substitute for CaM in binding to Cav2.1. However, structural distinctions between CaBP1 and CaM could underly distinct forms of Cav2.1 regulation. We tested this in whole-cell patch clamp recordings from tsA-201 cells cotransfected with cDNAs encoding CaBP1 and Cav2.1 channel subunits. CaBP1 significantly enhanced inactivation of Cav2.1 Ca2+ currents, caused a depolarizing shift in the voltage-dependence of activation, and prevented overt Ca2+-dependent facilitation of Cav2.1. Unlike the Ca2+-dependent modulation of Cav2.1 by CaM, these inhibitory effects of CaBP1 were observed with intracellular BAPTA and extracellular Ba2+, but not in Cav2.1 channels lacking the CBD. CaBP1 binding to the CBD was confirmed in yeast 2-hybrid and coimmunoprecipitation assays. Double-label immunocytochemistry of rat brain sections showed strong colocalization of CaBP1 and Cav2.1 in neuronal cell bodies and nerve terminals, particularly in the cerebellum. Our results reveal a novel Ca2+-independent inhibition of Cav2.1 mediated by a direct interaction with CaBP1 that may be physiologically relevant in controlling synaptic output through the negative regulation of presynaptic Ca2+ influx. Supported by grants from the National Institutes of Health (NS 22625 and NS 10645).
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2001 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2001. Online.
Copyright © 2001-2025 Society for Neuroscience; all rights reserved. Permission to republish any abstract or part of any abstract in any form must be obtained in writing by SfN office prior to publication.
