Potassium, M3 muscarinic receptors, and dopamine release

AbstractThe factors determining dopamine (DA) release induced by muscarinic receptor stimulation were investigated. Carbachol facilitated DA release elicited by electrical stimulation (1Hz, 2 min). In addition, carbachol per se induced DA release (direct action); an effect dependent of potassium levels. Increasing potassium from 4.8 to 12.5 mM produced a 10‐fold increase in carbachol‐induced DA release (P<0.001). DA release induced by electrical stimulation was not dependent on potassium levels. Low extracellular calcium (0.65 mM) reduced 44 ± 7 and 2 ± 1% the release evoked by electrical stimulation and carbachol, respectively (P<0.001). Tetrodotoxin (0.33 μM) inhibited the electrically‐evoked release by ≥ 90% and carbachol‐induced release by only 20% (P<0.001). Nomifensine (3 μM) and sulpiride (1 μM) enhanced carbachol‐induced DA release. The following order of potency: 4‐DAMP > pirenzepine > tropicamide > AF‐DX 116, was obtained for inhibiting carbachol‐induced DA release. In conclusion, carbachol acting through M3‐like (M1 possibly) muscarinic receptors induces the release of DA which is strongly dependent on extracellular potassium. This release seems of exocytotic nature, it is not dependent on the generation of action potentials and partly relies on intracellular calcium. Potassium level is a critical determinant of DA release mediated by M3 muscarinic receptor stimulation.