Aconitine facilitates spontaneous transmitter release at rat ventromedial hypothalamic neurons

Abstract

1 The eects 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 (3610 76 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, 3610 77 M) completely abolished the aconitine action on spontaneous IPSC frequency. Likewise removal of extracellular Na + completely suppressed the aconitine action. 5 Both Ca 2+ -free external solution or addition of 10 74 M Cd 2+ to normal solutions eliminated the facilitatory eect 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 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.

Ethanol Enhances Glutamate Transmission by Retrograde Dopamine Signaling in a Postsynaptic Neuron/Synaptic Bouton Preparation From the Ventral Tegmental Area

“…After 20 min, isolated neurons that adhered to the bottom of the dish were used for electrophysiological recordings. These mechanically dissociated neurons often preserved some functional nerve terminals, including those that release glutamate (Yamanaka et al , 2002; Akaike and Moorhouse, 2003; Ye et al , 2004; Zhu and Lovinger, 2005; Jang et al , 2006). …”

Crystal structure of tuguaconitine, a diterpene alkaloid from Aconitum sibiricum

“…1 to figure out its three-dimensional shape in space for the researchers. The imagination of its spatial shape of the molecule will clearly help the researchers in understanding the toxic interaction of aconitines with tetrodotoxinsensitive Na + channel (Yamanaka et al, 2002). There are two intermolecular hydrogen bonds which stabilize the molecular packing of tuguaconitine in the crystal.…”

“…al., , 1986. Aconitum alkaloids are potent neurotoxin known to activate voltage-dependent Na + channels, and there are trials to understand the molecular mode of action for the physiological effects of the compounds (Lao et al, 1990;Almanza et al, 1997;Yamanaka et al, 2002). However, it is very hard to imagine the overall shape of the molecule from the ordinary 2D-diagram (Fig.…”

Circadian aspects of hyperthermia in mice induced by Aconitum napellus

“…[ 46 ] Specialized neurophysiological research, based on patch-clamp techniques mainly related to the neuron excitability process, has demonstrated that a low physiological Acn dose (10 −6 M) affects individual pre-synaptic rat neuron excitability by opening Na+ channels. [ 47 ]…”