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Published on: May 10, 2012
Neurokinin-1 receptor activation in globus pallidus
Lei Chen1, Qiao-Ling Cui, Wing-Ho Yung
1School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin Hong Kong, China.
Frontiers in Neuroscience
|June 29, 2010
Summary
Neurokinin-1 receptor activation in the globus pallidus directly excites neurons by suppressing potassium conductance. This excitation may contribute to substance P
Area of Science:
- Neuroscience
- Electrophysiology
- Neuropharmacology
Background:
- Substance P, an undecapeptide, modulates neuronal activity via neurokinin-1 receptors.
- Neurokinin-1 receptors are present in the rat globus pallidus.
- The electrophysiological effects of neurokinin-1 receptor activation in this region are not well understood.
Purpose of the Study:
- To investigate the electrophysiological effects of neurokinin-1 receptor activation in rat globus pallidus neurons.
- To elucidate the ionic mechanisms underlying these effects.
- To examine the impact on GABAergic and glutamatergic neurotransmission.
Main Methods:
- Whole-cell patch-clamp recordings (current-clamp and voltage-clamp) were performed on globus pallidus neurons.
- Neurokinin-1 receptor agonist ([Sar9, Met(O2)11] substance P) and antagonist (SR140333B) were used.
- Experiments were conducted in the presence of glutamate and GABA receptor antagonists and tetrodotoxin.
Main Results:
- The neurokinin-1 receptor agonist depolarized globus pallidus neurons and increased their firing rate.
- This effect was postsynaptic, voltage-independent, and blocked by the antagonist.
- Suppression of potassium conductance was the primary ionic mechanism; spontaneous inhibitory postsynaptic current frequency increased.
Conclusions:
- Neurokinin-1 receptor activation directly excites globus pallidus neurons.
- This excitation is mediated by a reduction in potassium conductance.
- These findings suggest a role for neurokinin-1 receptor activation in the globus pallidus in the therapeutic effects of substance P in Parkinson's disease.
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