Regional differences in nerve terminal Na+ channel subtype expression and Na+ channel-dependent glutamate and GABA release in rat central nervous system

• Published in: Journal of neurochemistry Vol. 113; no. 6; pp. 1611 - 1620
• Main Authors: Westphalen, Robert I., Yu, Jieying, Krivitski, Margarita, Jih, Ting-Yu, Hemmings, Hugh C.
• Format: Journal Article
• Language: English
• Published: 29.03.2010
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2010.06722.x

We tested the hypothesis that expression of presynaptic voltage-gated Na + 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 [ 3 H]glutamate and [ 14 C]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 were similar 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.