Title : Activation of the recombinant human alpha 7 nicotinic acetylcholine receptor significantly raises intracellular free calcium - Delbono_1997_J.Pharmacol.Exp.Ther_280_428 |
Author(s) : Delbono O , Gopalakrishnan M , Renganathan M , Monteggia LM , Messi ML , Sullivan JP |
Ref : Journal of Pharmacology & Experimental Therapeutics , 280 :428 , 1997 |
Abstract :
The alpha 7 nicotinic acetylcholine receptor (nAChR) subtype, unlike other neuronal nicotinic receptors, exhibits a relatively high permeability to Ca++ ions. Although Ca++ entry through this receptor subtype has been implicated in various Ca(++)-dependent processes in the central nervous system, little is known about how this receptor modulates mammalian intracellular Ca++ dynamics. Intracellular Ca++ responses evoked by activation of the human alpha 7 nAChRs stably expressed in HEK-293 (human embryonic kidney) cells were studied. Inward current and intracellular Ca++ transients were recorded simultaneously in response to a fast drug application system. Current recordings under whole-cell voltage-clamp and fast ratiometric intracellular Ca++ imaging acquisition were synchronized to drug pulses. The mean peak [Ca++]i observed with 100 microM (-)-nicotine was 356 +/- 48 nM (n = 8). The magnitude of the intracellular Ca++ elevation corresponds to a 20% fractional current carried by Ca++ ions. The EC50 of the intracellular Ca++ responses for (-)-nicotine, (+/-)-epibatidine, 1,1 dimethyl-4-phenyl-piperazinium and acetylcholine were 51, 3.5, 75 and 108 microM, respectively. These EC50 values strongly correlate with those recorded for the cationic inward current through alpha 7 nAChR. alpha-Bungarotoxin, methyllcaconitine or extracellular Ca++ chelation ablated (-)-nicotine-evoked increase in intracellular Ca++ concentration. This study provides evidence that cation influx through the human alpha 7 nAChR is sufficient to mediate a significant, transient, rise in intracellular Ca++ concentration. |
PubMedSearch : Delbono_1997_J.Pharmacol.Exp.Ther_280_428 |
PubMedID: 8996225 |
Delbono O, Gopalakrishnan M, Renganathan M, Monteggia LM, Messi ML, Sullivan JP (1997)
Activation of the recombinant human alpha 7 nicotinic acetylcholine receptor significantly raises intracellular free calcium
Journal of Pharmacology & Experimental Therapeutics
280 :428
Delbono O, Gopalakrishnan M, Renganathan M, Monteggia LM, Messi ML, Sullivan JP (1997)
Journal of Pharmacology & Experimental Therapeutics
280 :428