PRESYNAPTIC AND POSTSYNAPTIC MUSCARINIC RECEPTORS IN THIN SLICES OF RAT ADRENAL-GLAND

The effects of activation of muscarinic receptors on chromaffin cells and splanchnic nerve terminals were studied in a rat adrenal slice pre paration. In chromaffin cells, muscarine induced a transient hyperpola rization followed by a depolarization associated with cell spiking. Th e hyperpolarization was blocked by charybdotoxin (1 mu M) and tetraeth ylammonium chloride (TEA, 1 mM), but was not affected by 200 mu M Cd2 or removal of external Ca2+ consistent with activation of BK channels . This would follow internal Ca2+ mobilization, as shown by Ca2+ imagi ng with fura-2 on isolated chromaffin cells in culture. Under voltage- clamp, outward BK currents were insensitive to MT3 toxin, a specific m uscarinic m4 receptor antagonist. In contrast, muscarine-induced depol arization was due to a m4 receptor-mediated inward current blocked by MT3 toxin. This current was permeable to cations and was associated wi th Ca2+ entry and subsequently, Ca2+-induced Ca2+ release. Finally, bo th muscarine (25 mu M) and oxotremorine (10 mu M) decreased the amplit ude and frequency of KCl-evoked excitatory postsynaptic currents, with out affecting quantal size, consistent with a presynaptic inhibitory e ffect. Taken together, our data suggest that activation of m4 and prob ably m3 muscarinic receptors results in a strong, long-lasting excitat ion of chromaffin cells, as well as an uncoupling of synaptic inputs o nto these cells.