Aconitine facilitates spontaneous transmitter release at rat ventromedial hypothalamic neurons.
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. Under current-clamp conditions, aconitine (3 x 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. Under the voltage-clamp conditions, aconitine reversibly increased the frequency of spontaneous IPSC and EPSC frequency, but it did not alter their amplitude distribution. Tetrodotoxin (TTX, 3 x 10(-7) M) completely abolished the aconitine action on spontaneous IPSC frequency. Likewise removal of extracellular Na(+) completely suppressed the aconitine action. Both Ca(2+)-free external solution or addition of 10(-4) M Cd(2+) to normal solutions eliminated the facilitatory effect of aconitine on the IPSC frequency. Overall these results suggest that aconitine depolarizes the presynaptic membrane by activating voltage-dependent Na(+) channels. Increase of intraterminal Ca(2+) concentration via an activation of voltage-dependent Ca(2+) 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.
Yamanaka
Hisashi
H
Cellular and System Physiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Doi
Atsushi
A
Ishibashi
Hitoshi
H
Akaike
Norio
N
D000157:Aconitine / Q000494:pharmacology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D014697:Ventromedial Hypothalamic Nucleus / Q000187:drug effects* / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D018377:Neurotransmitter Agents; D000157:Aconitine