Abstract
The undecapeptide substance P has been demonstrated to modulate neuronal activity in a number of brain regions by acting on neurokinin-1 receptors. Anatomical studies revealed a moderate level of neurokinin-1 receptor in rat globus pallidus. To determine the electrophysiological effects of neurokinin-1 receptor activation in globus pallidus, whole-cell patch-clamp recordings were performed in the present study. Under current-clamp recordings, neurokinin-1 receptor agonist, [Sar9, Met(O2)11] substance P (SM-SP) at 1 μM, depolarized globus pallidus neurons and increased their firing rate. Consistently, SM-SP induced an inward current under voltage-clamp recording. The depolarization evoked by SM-SP persisted in the presence of tetrodotoxin, glutamate and GABA receptor antagonists, indicating its direct postsynaptic effects. The neurokinin-1 receptor antagonist, SR140333B, could block SM-SP-induced depolarization. Further experiments showed that suppression of potassium conductance was the predominant ionic mechanism of SM-SP-induced depolarization. To determine if neurokinin-1 receptor activation exerts any effects on GABAergic and glutamatergic neurotransmission, the action of SM-SP on synaptic currents was studied. SM-SP significantly increased the frequency of spontaneous inhibitory postsynaptic currents, but only induced a transient increase in the frequency of miniature inhibitory postsynaptic currents. No change was observed in both spontaneous and miniature excitatory postsynaptic currents. Based on the direct excitatory effects of SM-SP on pallidal neurons, we hypothesize that neurokinin-1 receptor activation in globus pallidus may be involved in the beneficial effect of substance P in Parkinson's disease.
Highlights
Substance P, a widely distributed undecapeptide, has been established as a neurotransmitter or neuromodulator in central nervous system
In rats aged 14 days, a large number of substance P receptor immunoreactive neurons were found in globus pallidus. Most of these neurons were multipolar or fusiform in DISCUSSION The aim of this study was to determine the cellular action of substance P in the globus pallidus
We found that the neurokinin-1 receptor agonist, SM-SP, depolarized globus pallidus neurons
Summary
Substance P, a widely distributed undecapeptide, has been established as a neurotransmitter or neuromodulator in central nervous system. In terms of cellular actions, previous electrophysiological studies have demonstrated that substance P can enhance firing rate and depolarized neurons in several brain areas (Stanfield et al, 1985; Norris et al, 1993; Shirakawa and Moore, 1994; Napier et al, 1995; Minabe et al, 1996; Li and Guyenet, 1997; Wang and Robertson, 1997, 1998; Mitrovic and Napier, 1998; Preston et al, 2000; Bailey et al, 2004) It is generally regarded as an excitatory neurotransmitter or neuromodulator. Substance P has been reported to depolarize cholinergic and somatostatinergic interneurons (Aosaki and Kawaguchi, 1996)
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