Characterization of splice variations in the EF-hand of the Cav 2.1 P/Q - Type voltage-gated Calcium channel in the Central Nervous System

Abstract

Alternative splicing of a pair of mutually exclusive exons (exon 37a and 37b) of the P/Q-type Ca2+ channels produces two different splice variants in the EF-hand region, namely Cav2.1[EFa] and Cav2.1[EFb] channels. Using isoform-specific antibodies against Cav2.1[EFa] and Cav2.1[EFb] channels, we show that Cav2.1[EFa] and Cav2.1[EFb] channels are differentially localized in subcellular compartments of hippocampal, cerebellar and cortical neurons. Cav2.1[EFb] channels show somatic, proximal and distal dendritic localization while Cav2.1[EFa] channels are expressed in the cell bodies, proximal dendrites as well as presynaptic terminals. The distinct subcellular localization of Cav2.1[EFa] and Cav2.1[EFb] channels suggests compartmentalized roles of voltage-gated Ca2+ channels in neurotransmitter release and generation of synaptic plasticity. In addition, a yeast-two-hybrid screen was performed to find potential interacting proteins with the EF-hand of the Cav2.1[EFa] channel. The screen reveals possible modular and regulatory components of Calcium channels, which would greatly increase the repertoire of Ca2+ signaling in the neuron.