Potassium, M3 muscarinic receptors and dopamine release

The factors determining dopamine (DA) release induced by muscarinic recepto r stimulation were investigated. Carbachol facilitated DA release elicited by electrical stimulation (1Hz, 2 min). In addition, carbachol per se induc ed DA release (direct action); an effect dependent of potassium levels. Inc reasing potassium from 4.8 to 12.5 mM produced a 10-fold increase in carbac hol-induced DA release (P<0.001). DA release induced by electrical stimulat ion was not dependent on potassium levels. Low extracellular calcium (0.65 mM) reduced 44 +/- 7 and 2 +/- 1% the release evoked by electrical stimulat ion and carbachol, respectively (P<0.001). Tetrodotoxin (0.33 muM) inhibite d the electrically-evoked release by greater than or equal to 90% and carba chol-induced release by only 20% (P<0.001). Nomifensine (3 <mu>M) and sulpi ride (1 muM) enhanced carbachol-induced DA release. The following order of potency: 4-DAMP> pirenzepine > tropicamide> AF-DX 116, was obtained for inh ibiting carbachol-induced DA release. In conclusion, carbachol acting throu gh M3-like (M1 possibly) muscarinic receptors induces 1:he release of DA wh ich is strongly dependent on extracellular potassium. This release seems of exocytotic nature, it is not dependent on the generation of action potenti als and partly relies on intracellular calcium. Potassium level is a critic al determinant of DA release mediated by M3 muscarinic receptor stimulation .