Decrease heart rate and cardiac output How?- Acetylcholine binds to the M2 receptor in the heart activating Gi (GPCR), which will eventually lead to the hyperpolarization of the cell, because it opens the K+ channels and allows the K+ to leave the cell (makes the intercellular environment more negative).Recall that the Vagus nerve originates from cranial nerve X, which branches to the heart and lungs and the GI-tract (see figure).???