On the role of Ca2+ in the transmitter choice made by cultured sympathetic neurons

摘要: Depolarization or neuronal activity influences the differentiation of neonatal rat sympathetic neurons in dissociated cell culture by reducing their ability to respond a cholinergic factor in conditioned medium (CM), allowing adrenergic proceed (Walicke, P., R Campenot, and P. Patterson (1977) Proc. Natl. Acad. Sci. U. S. A. 74: 5767-5771). The present study analyzes the role Ca2+ mechanism this effect activity. Addition Ca2 + influx inhibitors, MgCb, D600, diphenylhydantoin (DPH), EGTA growth overcomes developmental effect depolarization. Elevation CaCb level medium, addition BaCh, slightly enhances In non-depolarized cultures, Ba2+ potently inhibits cholinergic and additional has similar, though smaller, effect. Chronic depolarization neurons with either elevated K+ veratridine leads an increase cyclic AMP (cAMP) content, elevation is blocked, along on transmitter choice, by MgCb D600. On other hand, (ethylene glycol bis(,8-aminoethyl ether)-N,N'-tetraacetic acid) DPH, which also favor differentiation, have little depolarization- induced cAMP. Exogenous cyclic nucleotide derivatives prostaglandin Ei, like depolarization, decrease induction. EGTA, however, decreases the developmental effects these agents while not interfering cAMP levels. Thus, there are several ways cAMP levels can be uncoupled from choice. The inhibitors counteract depolarization development and probably does reflect blockade action interposed neurotransmitter, since phentolamine, phenoxybenzamine, adenosine deaminase, alloxazine have no choice levels. Although calcium undoubtedly have complex interactions neurons, appears play major developmental effects intracellular events governing choice.