Abstract
I had suggested that muscarine presynaptically inhibited the GABAergic IPSC at a putative striato-nigral “direct” pathway on a substantia nigra pars reticulata (SNr) GABA neurons through the activation of M3-muscarinic acetylcholine (ACh) receptor, as 4-DAMP abolished the inhibition. However, GF109203X (1 μM, a previous result), ryanodine (200 nM & 20 μM, n=4 in each concentration), thapsigargin (5 μM, n=3) and apamin (1 μM, n=4) did not have any significant inhibitory effects on this IPSC inhibition by muscarine (10 μM). These results might indicate that the M1-, M3- or M5-receptors activation did not induce the inhibition. I had already reported that a M2-receptors antagonist, AF-DX116 (300 nM), did not affect the inhibition. Therefore, the relation between the M4-receptor activation and this inhibition was investigated, in this time. Forskolin (10 μM) significantly decreased this IPSC inhibition by muscarine (p<0.005, n=6). In the solution with a M4-receptor selective antagonist, muscarine toxin-3 (MT-3), the IPSC inhibition was dose-dependently decreased. The inhibition ratio, which was calculated by the equation of “1 – an amplitude of IPSC in the muscarine solution / a control IPSC amplitude”, was decreased from 0.56 to 0.32 in the solution with 30 nM MT-3. These results may suggest that the activation of the M3-muscarinic ACh receptor dose not induce the presynaptic inhibition of a putative striato-nigral GABAergic IPSC at SNr GABA neurons by muscarine, but the M4-receptor activation induces it. [Jpn J Physiol 55 Suppl:S155 (2005)]
