Regional differences in nerve terminal Na plus channel subtype expression and Na plus channel-dependent glutamate and GABA release in rat CNS

P>We tested the hypothesis that expression of pre-synaptic voltage-gated sodium channel (Na-v) subtypes coupled to neurotransmitter release differs between transmitter types and CNS regions in a nerve terminal-specific manner. Na-v coupling to transmitter release was determined by measuring the sensitivity of 4-aminopyridine (4AP)-evoked [3H]glutamate and [14C]GABA release to the specific Na-v blocker tetrodotoxin (TTX) for nerve terminals isolated from rat cerebral cortex, hippocampus, striatum and spinal cord. Expression of various Na-v subtypes was measured by immunoblotting using subtype-specific antibodies. Potencies of TTX for inhibition of glutamate and GABA release varied between CNS regions. However, the efficacies of TTX for inhibition of 4AP-evoked glutamate release were greater than for inhibition of GABA release in all regions except spinal cord. The relative nerve terminal expression of total Na-v subtypes as well as of specific subtypes varied considerably between CNS regions. The region-specific potencies of TTX for inhibition of 4AP-evoked glutamate release correlated with greater relative expression of total nerve terminal Na-v and Na(v)1.2. Nerve terminal-specific differences in the expression of specific Na-v subtypes contribute to transmitter-specific and regional differences in pharmacological sensitivities of transmitter release.