Mechanism for modulation of nicotinic acetylcholine receptors that can influence synaptic transmission.
Only recently has it been appreciated that neuronal nicotinic ACh receptors (NnAChRs) are highly permeable to Ca2+ and are modulated by Ca2+ in a dose-dependent manner. These findings suggest that Ca2+ could have roles in cholinergic synaptic plasticity. We report a possible mechanism for Ca(2+)-initiated synaptic plasticity that differs from the intracellular Ca2+ cascade associated with plasticity of glutamatergic synapses. Rapid changes in external Ca2+ modulate cholinergic spontaneous synaptic currents in superior cervical ganglionic sympathetic neurons. Inhibition of cholinergic currents by chlorisondamine, which blocks only open channels and becomes trapped in the pore, showed that the modulation is not by a mechanism that activates a previously unresponsive population of NnAChRs. Rather, single-channel recordings with ganglionic NnAChRs from chromaffin cells indicated that Ca2+ directly alters the probability of the channels being open. We hypothesize from the results that activity-dependent decreases in external Ca2+, which occur throughout the nervous system, could directly underlie a rapid negative-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 receptors until the external Ca2+ concentration recovers.
Amador
M
M
Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030-3498, USA.
Dani
J A
JA
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000494:pharmacology*; D002478:Cells, Cultured; D002714:Chlorisondamine / Q000494:pharmacology; D015640:Ion Channel Gating / Q000502:physiology; D007700:Kinetics; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011336:Probability; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology*; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D011978:Receptors, Nicotinic; D002714:Chlorisondamine; D002118:Calcium