Abstract
Although I have analyzed the mechanism of muscarinic inhibition on the IPSC at substantia nigra pars reticulata GABA neurons of rat, the intracellular transduction mechanism is not clear yet. N-ethylmaleimide (NEM), a membrane permeable inhibitor of PTX-sensitive G-proteins, did not have any significant effect on the muscarinic inhibition at the concentration of 100 μM. NEM itself significantly increased in the amplitude of IPSC to 1.627 ± 0.166 of the control amplitude (n=5, mean ± S.E.M., p=0.019 by Student's t test paired). Muscarine (10 μM) reduced the IPSC amplitude to 0.420 ± 0.104 under the control condition and to 0.370 ± 0.050 of the increased IPSC in the solution with NEM, respectively (p=0.738). ω-Agatoxin TK (ω-Aga TK), a selective P-type Ca2+ channel blocker, exerted no inhibitory influence on the muscarinic inhibition. The amplitude of IPSC was significantly attenuated to 0.443 ± 0.139 (n=4, p=0.031) in the solution with ω-Aga TK (100 nM). The muscarinic inhibition ratios were 0.430 ± 0.089 in control and 0.326 ± 0.077 of the decreased IPSC in the solution with ω-Aga TK, respectively (p=0.386). These results mentioned above and those previously reported suggest that Gβγ subunits dissociated from Gq/11 linked with M3-receptors reduce the GABA release through the direct effect on the release machinery, when M3-muscarinic ACh receptors at the presynaptic terminal of a striato-nigral projection fiber is activated. Hopefully, these observations contribute to the new approach of drug therapy for the basal ganglia disturbance. [J Physiol Sci. 2006;56 Suppl:S165]
