DIVERSITY OF NICOTINIC ACETYLCHOLINE-RECEPTORS IN RAT HIPPOCAMPAL-NEURONS .4. REGULATION BY EXTERNAL CA-BUNGAROTOXIN-SENSITIVE RECEPTOR FUNCTION AND OF RECTIFICATION INDUCED BY INTERNAL MG++(+ OF ALPHA)
R. Bonfantecabarcas et al., DIVERSITY OF NICOTINIC ACETYLCHOLINE-RECEPTORS IN RAT HIPPOCAMPAL-NEURONS .4. REGULATION BY EXTERNAL CA-BUNGAROTOXIN-SENSITIVE RECEPTOR FUNCTION AND OF RECTIFICATION INDUCED BY INTERNAL MG++(+ OF ALPHA), The Journal of pharmacology and experimental therapeutics, 277(1), 1996, pp. 432-444
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, i.e.,
the currents subserved by cr-bungarotoxin (alpha-BGT)-sensitive, alpha
-7-containing nicotinic acetylcholine receptors (nAChRs). The rundown
profile of acetylcholine (ACh)-induced type IA currents that were obta
ined using patch pipettes filled with F--based internal solution had t
wo components: the first component of rundown was counteracted by a mo
re physiological internal solution containing an organic anion (malate
or aspartate), suggesting energy dependence; the second component exh
ibited dependence on concentration of CaCl2 added to the external solu
tion ([Ca++](o)), with rundown minimized at 0.32 mM. The inward rectif
ication of ACh-elicited type IA currents, induced by intracellular Mg+ was augmented by lowering [Ca++](o) (from 2 to 0.32 mM). Moreover, e
xtracellular Ca++ (0.01-10 mM) acted in a concentration-dependent mann
er (IC50 = 0.26 mM) to decrease the cooperativity induced by ACh (n(H)
was reduced from 2.7 to 1). Extracellular Ca++ (EC(50) = 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-sensit
ive nAChRs (IC50 = 11 mM). In conclusion, Ca++ regulates agonist effic
acy and cooperativity at the alpha-BGT-sensitive neuronal nAChR, modul
ates rundown and counteracts Mg++-dependent inward rectification of ty
pe IA currents, It is suggested that the regulation by Ca++ of the alp
ha-BGT-sensitive nAChR activity could modulate many neuronal functions
.