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

• 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 Jr, Hugh C
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01-06-2010; Blackwell Publishing Ltd; Wiley-Blackwell
• Subjects: 4-Aminopyridine - pharmacology; Aniline Compounds - pharmacology; Animals; Biochemistry; Biological and medical sciences; Central nervous system; Central Nervous System - anatomy & histology; Central Nervous System - metabolism; Central neurotransmission. Neuromudulation. Pathways and receptors; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dose-Response Relationship, Drug; Drug Interactions; Fundamental and applied biological sciences. Psychology; Furans - pharmacology; gamma-Aminobutyric Acid - metabolism; Gene Expression - physiology; Glutamic Acid - metabolism; Male; Medical sciences; Neurology; neurotransmitter release; Neurotransmitters; Potassium Channel Blockers - pharmacology; pre-synaptic; Presynaptic Terminals - drug effects; Presynaptic Terminals - metabolism; Protein Subunits - metabolism; Rats; Rats, Sprague-Dawley; Rodents; Sodium; Sodium Channel Blockers - pharmacology; sodium channels; Sodium Channels - genetics; Sodium Channels - metabolism; tetrodotoxin; Tetrodotoxin - pharmacology; Veratridine - pharmacology; Vertebrates: nervous system and sense organs; Cerebral cortex; Rat; Rodentia; Central nervous system; Basal ganglion; Ionic channel; pre-synaptic; Glutamate; neurotransmitter release; Encephalon; Vertebrata; Sensitivity; Mammalia; Sodium; sodium channels; Voltage; Excitatory aminoacid; Neurotransmitter; Coupling; tetrodotoxin; Subtype; Hippocampus; Release
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2010.06722.x

J. Neurochem. (2010) 113, 1611-1620. We tested the hypothesis that expression of pre-synaptic voltage-gated sodium channel (Nav) subtypes coupled to neurotransmitter release differs between transmitter types and CNS regions in a nerve terminal-specific manner. Nav coupling to transmitter release was determined by measuring the sensitivity of 4-aminopyridine (4AP)-evoked [³H]glutamate and [¹⁴C]GABA release to the specific Nav blocker tetrodotoxin (TTX) for nerve terminals isolated from rat cerebral cortex, hippocampus, striatum and spinal cord. Expression of various Nav 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 Nav 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 Nav and Nav1.2. Nerve terminal-specific differences in the expression of specific Nav subtypes contribute to transmitter-specific and regional differences in pharmacological sensitivities of transmitter release.