MECHANISM FOR MODULATION OF NICOTINIC ACETYLCHOLINE-RECEPTORS THAT CAN INFLUENCE SYNAPTIC TRANSMISSION

Only recently has it been appreciated that neuronal nicotinic ACh rece ptors (NnAChRs) are highly permeable to Ca2+ and are modulated by Ca2 in a dose-dependent manner, These findings suggest that Ca2+ could ha ve roles in cholinergic synaptic plasticity, We report a possible mech anism for Ca2+-initiated synaptic plasticity that differs from the int racellular Ca2+ cascade associated with plasticity of glutamatergic sy napses, Rapid changes in external Ca2+ modulate cholinergic spontaneou s synaptic currents in superior cervical ganglionic sympathetic neuron s, Inhibition of cholinergic currents by chlorisondamine, which blocks only open channels and becomes trapped in the pore, showed that the m odulation is not by a mechanism that activates a previously unresponsi ve population of NnAChRs, Rather, single-channel recordings with gangl ionic NnAChRs from chromaffin cells indicated that Ca2+ directly alter s the probability of the channels being open, We hypothesize from the results that activity-dependent decreases in external Ca2+, which occu r throughout the nervous system, could directly underlie a rapid negat ive-feedback mechanism that decreases the responsiveness of NnAChRs at synapses, When external Ca2+ is decreased, presynaptic Ca2+ currents and transmitter release also are diminished, Thus, several mechanisms could combine to potently and rapidly depress synaptic nicotinic recep tors until the external Ca2+ concentration recovers.