P/Q-Type, But Not N-Type, Calcium Channels Mediate GABA Release From Fast-Spiking Interneurons to Pyramidal Cells in Rat Prefrontal Cortex

Abstract

The Cav2.1 (P/Q-) and Cav2.2 (N-type) voltage-gated calcium channels (VGCCs) play a predominant role in neurotransmitter release at central synapses, but their distribution is not uniform across different types of synapses. Although the functional significance of the differential distribution of N- and P/Q-type VGCCs is poorly understood, distinct types of VGCCs appear to differentially affect synaptic properties. For example, P/Q-type VGCCs are located closer to release sites and are less affected by G-protein-mediated inhibition than are N-type VGCCs. Thus P/Q-type VGCCs might be beneficial at synapses with high probability of release and precise timing of neurotransmission, such as the inhibitory inputs from parvalbumin-containing fast-spiking (FS) interneurons to pyramidal cells (PCs) in the neocortex. To determine whether VGCCs types predominate at synapses from FS interneurons to PCs in rat prefrontal cortex, whole cell paired recordings (n = 14) combined with intracellular labeling and fluorescence immunohistochemistry for parvalbumin were performed in acute slices. Bath application of the specific N-type VGCC blocker omega-conotoxin-GVIa (1 microM) did not alter inhibitory postsynaptic potential amplitude, failure rate, or synaptic dynamics; in contrast, application of P/Q-type VGCC blocker omega-agatoxin-IVa (0.5 microM) completely and irreversibly blocked neurotransmission. These results indicate that P/Q-type VGCCs mediate the GABA release from parvalbumin-positive FS interneurons to PCs in the rat neocortex.