title: Diversity of nicotinic acetylcholine receptors in rat hippocampal neurons. IV. Regulation by external Ca++ of alpha-bungarotoxin-sensitive receptor function and of rectification induced by internal Mg++.
abstract: Applying the whole-cell mode of the patch-clamp technique to cultured hippocampal neurons, we demonstrated that extracellular Ca++ modulates the activation and inactivation of type IA nicotinic currents, ie., the currents subserved by alpha-bungarotoxin (alpha-BGT)-sensitive, alpha-7-containing nicotinic acetylcholine receptors (nAChRs). The rundown profile of acetylcholine (ACh)-induced type IA currents that were obtained using patch pipettes filled with F(-)-based internal solution had two components: the first component of rundown was counteracted by a more physiological internal solution containing an organic anion (malate or aspartate), suggesting energy dependence; the second component exhibited dependence on concentration of CaCl2 added to the external solution ([Ca++]o), with rundown minimized at 0.32 mM. The inward rectification of Ach-elicited type IA currents, induced by intracellular Mg++ was augmented by lowering [Ca++]o (from 2 to 0.32 mM). Moreover, extracellular Ca++ (0.01-10 mM) acted in a concentration-dependent manner (IC50 = 0.26 mM) to decrease the cooperativity induced by ACh (nH was reduced from 2.7 to 1). Extracellular Ca++ (EC50 = 0.1 mM) also increased the efficacy of ACh, but exposure to [Ca++]o from 1 to 32 mM decreased the efficacy of ACh and inactivated the alpha-BGT-sensitive nAChRs (IC50 = 11 mM). In conclusion, Ca++ regulates agonist efficacy and cooperativity at the alpha-BGT-sensitive neuronal nAChR, modulates rundown and counteracts Mg++ -dependent inward rectification of type IA currents. It is suggested that the regulation by Ca++ of the alpha-BGT-sensitive nAChR activity could modulate many neuronal functions.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, USA.
authors.forename: R
authors.initials: R
authors.lastname: Bonfante-Cabarcas
authors.forename: K L
authors.initials: KL
authors.lastname: Swanson
authors.forename: M
authors.initials: M
authors.lastname: Alkondon
authors.forename: E X
authors.initials: EX
authors.lastname: Albuquerque
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000222:Adaptation, Physiological; D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology*; D006624:Hippocampus / Q000502:physiology*; D008274:Magnesium / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology*
chemical_list: D002038:Bungarotoxins; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D008274:Magnesium; D000109:Acetylcholine; D002118:Calcium