%0 Journal Article
%T Nicotinic Modulation of GABAA Receptor Function in Single Dopaminergic Neurons Freshly-Dissociated from Rat Substantia Nigra Pars Compacta
%A Jie Wu
%A Junfang Zhang
%A Kechun Yang
%J Open Journal of Immunology
%D -1
%R 10.4172/2167-0501.S1-003
%X Previous studies have shown that nicotine modulates GABAergic transmission onto dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNc) mainly via presynaptic mechanisms. However, nicotinic modulation of postsynaptic GABAA receptor function in SNc DAergic neurons is unknown. Employing patch-clamp recording technique in single putative DAergic neurons freshly dissociated from rat SNc, we found that functional ¦Á4¦Â2-nAChRs were well expressed on majority (77%) of putative SNc DAergic neurons recorded (type ID neurons), while functional ¦Á7-nAChRs were only detected in 23% of recorded putative SNc DAergic neurons (type IID neurons). Smoking relevant concentration of nicotine reversibly increased the amplitude of GABAA receptor-mediated wholecell
currents in 63% of type ID neurons expressing ¦Á4¦Â2-nAChRs, but not in those type IID neurons expressing ¦Á7-nAChRs, which suggests that postsynaptic GABAA receptors on putative SNc DAergic neurons that contain nAChR ¦Á4¦Â2 subunits are significantly modulated by nicotine. Interestingly, nicotine at concentrations from 1 nM to 10 ¦ÌM produced concentration-independent enhancement effects on GABAA receptor-mediated currents. There was no significant influence of pretreatment with either DH¦ÂE (a selective ¦Á4¦Â2-nAChR antagonist) or 500 nM nicotine over the nicotinic modulation. In addition, 500 nM nicotine did not affect glutamate or glycine-induced current under our experimental conditions. Collectively, our results suggest that nicotine directly boosts the function of postsynaptic
GABAA receptors, which in turn results in hyperpolarization and reduced excitability of putative SNc DAergic neurons through novel ¦Á4¦Â2-nAChR-dependent pathways and/or additional postsynaptic mechanisms
%K Kechun Yang
%K Junfang Zhang and Jie Wu
%K Nicotine
%K Nicotinic acetylcholine receptor
%K DAergic neuron
%K GABAA receptors
%K Substantia nigra pars compacta
%U https://www.longdom.org/abstract/nicotinic-modulation-of-gabaa-receptor-function-in-single-dopaminergic-neurons-freshlydissociated-from-rat-substantia-ni-7386.html