Requirement for the synaptic protein interaction site for reconstitution of synaptic transmission by P/Q-type calcium channels

Ca_v2.1 channels, which conduct P/Q-type Ca²⁺ currents, were expressed in superior cervical ganglion neurons in cell culture, and neurotransmission initiated by these exogenously expressed Ca²⁺ channels was measured. Deletions in the synaptic protein interaction (synprint) site in the intracellular loop between domains II and III of Ca_v2.1 channels reduced their effectiveness in synaptic transmission. Surprisingly, this effect was correlated with loss of presynaptic localization of the exogenously expressed channels. Ca_v1.2 channels, which conduct L-type Ca²⁺ currents, are ineffective in supporting synaptic transmission, but substitution of the synprint site from Ca_v2.1 channels in Ca_v1.2 was sufficient to establish synaptic transmission initiated by L-type Ca²⁺ currents through the exogenous Ca_v1.2 channels. Substitution of the synprint site from Ca_v2.2 channels, which conduct N-type Ca²⁺ currents, was even more effective than Ca_v2.1. Our results show that localization and function of exogenous Ca²⁺ channels in nerve terminals of superior cervical ganglion neurons require a functional synprint site and suggest that binding of soluble NSF attachment protein receptor(SNARE) proteins to the synprint site is a necessary permissive event for nerve terminal localization of presynaptic Ca²⁺ channels.