M1 receptors are highly expressed in both striatonigral and striatopallidal MSNs [20]. Unlike D1 and D2 dopamine receptors, the prevailing view is that M1 receptor activation does not directly regulate glutamatergic synapse function from the postsynaptic side. Studies of voltage-gated channels suggest M1 receptor activation excites MSNs by modulating potassium channels [22,23]. M1 receptor activation reduces opening of Kv4 channels (A-type potassium channels) and shifts their activation and inactivation voltage dependence [24] in a PKC dependent process [25]. In addition, M1 receptor activation coupled to PLCβ and PKC leads to membrane depletion of PIP2, which modulates subthreshold potassium conductances of Kv7 (M-channel, KCNQ) and Kir2 (inward-rectifying potassium channel) channels [26,27] all contributing to MSN depolarization.
