The α7 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 α7 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 μM (-)-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 μM, respectively. These EC50 values strongly correlate with those recorded for the cationic inward current through α7 nAChR. α-Bungarotoxin, methyllcaconitine or extracellular Ca++ chelation ablated (-)-nicotine- evoked increase in intracellular Ca++ concentration. This study provides evidence that cation influx through the human α7 nAChR is sufficient to mediate a significant, transient, rise in intracellular Ca++ concentration.
|Original language||English (US)|
|Number of pages||11|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - May 3 1997|
ASJC Scopus subject areas
- Molecular Medicine