title: Inhibition of membrane Na+ channels by A type botulinum toxin at femtomolar concentrations in central and peripheral neurons.
abstract: Recent studies have demonstrated that the botulinum neurotoxins inhibit the release of acetylcholine, glutamate, GABA, and glycine in central nerve system (CNS) neurons. The Na(+) current (I(Na)) is of major interest because it acts as the trigger for many cellular functions such as transmission, secretion, contraction, and sensation. Thus, these observations raise the possibility that A type neurotoxin might also alter the I(Na) of neuronal excitable membrane. To test our idea, we examined the effects of A type neurotoxins on I(Na) of central and peripheral neurons. The neurotoxins in femtomolar to picomolar concentrations produced substantial decreases of the neuronal I(Na), but interestingly the current inhibition was saturated at about maximum 50% level of control I(Na). The inhibitory pattern in the concentration-response curve for the neurotoxins differed from tetrodotoxin (TTX), local anesthetic, and antiepileptic drugs that completely inhibited I(Na) in a concentration-dependent manner. We concluded that A type neurotoxins inhibited membrane Na(+)-channel activity in CNS neurons and that I(Na) of both TTX-sensitive and -insensitive peripheral dorsal ganglion cells were also inhibited similarly to a maximum 40% of the control by the neurotoxins. The results suggest evidently that A2NTX could be also used as a powerful drug in treating epilepsy and several types of pain.
authors.affiliation: Research Division for Life Sciences, Kumamoto Health Science University, Japan.
authors.forename: Min-Chul
authors.initials: MC
authors.lastname: Shin
authors.forename: Masahito
authors.initials: M
authors.lastname: Wakita
authors.forename: Du-Jie
authors.initials: DJ
authors.lastname: Xie
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Yamaga
authors.forename: Satomi
authors.initials: S
authors.lastname: Iwata
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Torii
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Harakawa
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ginnaga
authors.forename: Shunji
authors.initials: S
authors.lastname: Kozaki
authors.forename: Norio
authors.initials: N
authors.lastname: Akaike
mesh_terms: D000818:Animals; D019274:Botulinum Toxins, Type A / Q000494:pharmacology*; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000502:physiology*; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009498:Neurotoxins / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D009498:Neurotoxins; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013779:Tetrodotoxin; D019274:Botulinum Toxins, Type A