Abstract
Active zones (AZs) are highly specialized sites for release of neurotransmitter in presynaptic nerve terminals. The spacing between voltage-dependent calcium channels (VDCCs) and synaptic vesicles at AZs is thought to influence the dynamic properties of synaptic transmission. However, molecular determinants that maintain or regulate appropriate distance between vesicles and VDCCs have been elusive. Recently we have demonstrated a novel molecular interaction between an AZ scaffolding protein and VDCCs. To elucidate the functional significance of this direct coupling, we characterized whole-cell Ba2+ currents through recombinant P/Q-type VDCC expressed as α1Aα2/δβ1a complex in baby hamster kidney cells. The AZ protein induced a pronounced deceleration of inactivation rate and a depolarizing shift of the inactivation curve. During 2-s voltage-displacement to -30 mV, which is the threshold of the P/Q-type VDCC activation, almost all of the channels were inactivated in the absence of the AZ protein (closed-state inactivation), but less than 20% of the channels were inactivated in the presence of the AZ protein. Currents evoked by trains of action potential waveforms, a more physiological voltage-clamp protocol used particularly to reveal closed-state inactivation, further support profound suppression of voltage-dependent inactivation by the AZ protein. Thus, the AZ protein coordinates calcium signaling and spatial organization of molecular constituents in presynaptic AZ. [J Physiol Sci. 2007;57 Suppl:S224]
