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J Am Coll Surg. 1996 Jun;182(6):473-81.

Acetylcholine-induced calcium signaling associated with muscarinic receptor activation in cultured myenteric neurons.

Author information

1
Department of Surgery, University of Michigan School of Medicine, Ann Arbor, USA.

Abstract

BACKGROUND:

Within the enteric nervous system, acetylcholine (ACh) is an important neurotransmitter. Experimental evidence has suggested that in myenteric neurons, calcium plays a key role in the coupling of cholinergic receptors to secretory responses.

STUDY DESIGN:

We investigated the effects of ACh on intracellular calcium concentration ([Ca2+]i) in individual myenteric neurons using fura-2 microspectrofluorometry.

RESULTS:

Resting [Ca2+]i in myenteric neurons was 62.5 +/- 3 nM. Acetylcholine produced dose-dependent increases in [Ca2+]i in myenteric neurons. As the concentration of ACh was increased from 0.1 to 100 microM, both the peak [Ca2+]i response as well as the percentage of responding neurons progressively increased, with a maximal effect at 100 microM (347 +/- 31 nM, 95 percent of neurons). The effect of ACh was not sensitive to pertussis toxin (100 ng/mL). Calcium ion (Ca2+) responses to ACh were abolished by removal of extracellular Ca2+ as well as exposure to nifedipine (10 microM). Characterization of the specific muscarinic subtype(s) involved in ACh-mediated Ca2+ transients was performed using the specific antagonists pirenzepine (M1), gallamine (M2), and 4-DAMP (M3). Pirenzepine (1 microM) blocked increases in [Ca2+]i induced by ACh; gallamine (1 microM) and 4-DAMP (1 microM) had no significant effect. Intracellular Ca2+ responses to ACh were not affected by incubation with the phorbol ester tetradecanoylphorbol-13-acetate (1 microM).

CONCLUSIONS:

These findings suggest that ACh induces increases in [Ca2+]i in myenteric neurons by promoting influx of extracellular Ca2+ through L-type voltage-dependent Ca2+ channels by activation of the M1 muscarinic receptor subtype. The Ca2+ response does not appear to involve a pertussis toxin-sensitive G protein.

PMID:
8646346
[Indexed for MEDLINE]
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