Aconitine facilitates spontaneous transmitter release at rat ventromedial hypothalamic neurons

Hisashi Yamanaka, Atsushi Doi, Hitoshi Ishibashi, Norio Akaike

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

1. The effects of aconitine, an Aconitum alkaloid, on spontaneous inhibitory and excitatory postsynaptic currents (IPSCs and EPSCs respectively) were investigated in the mechanically dissociated rat ventromedial hypothalamic (VMH) neurons in which native presynaptic nerve terminals remained intact. 2. Under current-clamp conditions, aconitine (3 × 10-6 M) depolarized the neuron with generating the action potentials. The aconitine-induced depolarization was markedly suppressed in the presence of CNQX but it was facilitated in the presence of bicuculline, suggesting that release of excitatory and inhibitory neurotransmitters may be involved in the aconitine action in addition to its direct action on postsynaptic membrane. 3. Under the voltage-clamp conditions, aconitine reversibly increased the frequency of spontaneous IPSC and EPSC frequency, but it did not alter their amplitude distribution. 4. Tetrodotoxin (TTX, 3 × 10-7 M) completely abolished the aconitine action on spontaneous IPSC frequency. Likewise removal of extracellular Na+ completely suppressed the aconitine action. 5. Both Ca2+-free external solution or addition of 10-4 M Cd2+ to normal solutions eliminated the facilitatory effect of aconitine on the IPSC frequency. 6. Overall these results suggest that aconitine depolarizes the presynaptic membrane by activating voltage-dependent Na+ channels. Increase of intraterminal Ca2+ concentration via an activation of voltage-dependent Ca2+ channels in turn enhances the spontaneous transmitter release from presynaptic nerve terminals. The presynaptic action of aconitine may play a crucial role for membrane excitability of rat VMH neurons.

Original languageEnglish
Pages (from-to)816-822
Number of pages7
JournalBritish Journal of Pharmacology
Volume135
Issue number3
DOIs
Publication statusPublished - Jan 1 2002

All Science Journal Classification (ASJC) codes

  • Pharmacology

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