Referenced in: none

Automatically associated channels: Cav2.2

Title: Inhibition of synaptic transmission and G protein modulation by synthetic CaV2.2 Ca2+ channel peptides.

Authors: Giovanna Bucci, Sumiko Mochida, Gary J Stephens

Journal, date & volume: J. Physiol. (Lond.), 2011 Jul 1 , 589, 3085-101

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21521766

Abstract
Modulation of presynaptic voltage-dependent Ca2+ channels is a major means of controlling neurotransmitter release. The CaV2.2Ca2+ channel subunit contains several inhibitory interaction sites for Gβγ subunits, including the amino terminal (NT) and I-II loop. The NT and I-II loop have also been proposed to undergo a G protein-gated inhibitory interaction, whilst the NT itself has also been proposed to suppress CaV2 channel activity. Here, we investigate the effects of an amino terminal (CaV2.2[45-55]) 'NT peptide' and a I-II loop alpha interaction domain (CaV2.2[377-393]) 'AID peptide' on synaptic transmission, Ca2+ channel activity and G protein modulation in superior cervical ganglion neurones (SCGNs). Presynaptic injection of NT or AID peptide into SCGN synapses inhibited synaptic transmission and also attenuated noradrenaline-induced G protein modulation. In isolated SCGNs, NT and AID peptides reduced whole-cell Ca2+ current amplitude, modified voltage dependence of Ca2+ channel activation and attenuated noradrenaline-induced G protein modulation. Co-application of NT and AID peptide negated inhibitory actions. Together, these data favour direct peptide interaction with presynaptic Ca2+ channels, with effects on current amplitude and gating representing likely mechanisms responsible for inhibition of synaptic transmission. Mutations to residues reported as determinants of Ca2+ channel function within the NT peptide negated inhibitory effects on synaptic transmission, Ca2+ current amplitude and gating and G protein modulation. A mutation within the proposed QXXER motif for G protein modulation did not abolish inhibitory effects of the AID peptide. This study suggests that the CaV2.2 amino terminal and I-II loop contribute molecular determinants for Ca2+ channel function; the data favour a direct interaction of peptides with Ca2+ channels to inhibit synaptic transmission and attenuate G protein modulation.