Background5-hydroxytryptamine (5-HT) is one of the major neurotransmitters widely distributed in the CNS. Several 5-HT receptor subtypes have been identified in the spinal dorsal horn which act on both pre- and postsynaptic sites of excitatory and inhibitory neurons. However, the receptor subtypes and sites of actions as well as underlying mechanism are not clarified rigorously. Several electrophysiological studies have been performed to investigate the effects of 5-HT on excitatory transmission in substantia gelatinosa (SG) of the spinal cord. In the present study, to understand the effects of 5-HT on the inhibitory synaptic transmission and to identify receptor subtypes, the blind whole cell recordings were performed from SG neurons of rat spinal cord slices.ResultsBath applied 5-HT (50 μM) increased the frequency but not amplitudes of spontaneous inhibitory postsynaptic currents (sIPSCs) in 58% of neurons, and both amplitude and frequency in 23% of neurons. The frequencies of GABAergic and glycinergic mIPSCs were both enhanced. TTX (0.5 μM) had no effect on the increasing frequency, while the enhancement of amplitude of IPSCs was eliminated. Evoked-IPSCs (eIPSCs) induced by focal stimulation near the recording neurons in the presence of CNQX and APV were enhanced in amplitude by 5-HT. In the presence of Ba2+ (1 mM), a potassium channel blocker, 5-HT had no effect on both frequency and amplitude. A 5-HT2A receptor agonist, TCB-2 mimicked the 5-HT effect, and ketanserin, an antagonist of 5-HT2A receptor, inhibited the effect of 5-HT partially and TCB-2 almost completely. A 5-HT2C receptor agonist WAY 161503 mimicked the 5-HT effect and this effect was blocked by a 5-HT2C receptor antagonist, N-desmethylclozapine. The amplitudes of sIPSCs were unaffected by 5-HT2A or 5-HT2C agonists. A 5-HT3 receptor agonist mCPBG enhanced both amplitude and frequency of sIPSCs. This effect was blocked by a 5-HT3 receptor antagonist ICS-205,930. The perfusion of 5-HT2B receptor agonist had no effect on sIPSCs.ConclusionsOur results demonstrated that 5-HT modulated the inhibitory transmission in SG by the activation of 5-HT2A and 5-HT2C receptors subtypes located predominantly at inhibitory interneuron terminals, and 5-HT3 receptors located at inhibitory interneuron terminals and soma-dendrites, consequently enhanced both frequency and amplitude of IPSCs.

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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.