Muscarinic stimulation increases Na+ entry in pancreatic B-cells by a mechanism other than the emptying of intracellular Ca2+ pools.
Stimulation of muscarinic (M3) receptors depolarizes pancreatic B-cells by increasing Na+ influx. Here, we measured [Na+]i and [Ca2+]i in B-cell clusters to investigate whether depletion of intracellular Ca2+ pools triggers this unusual transduction pathway for muscarinic receptors. Acetylcholine emptied Ca2+ pools less completely than did the SERCA pump inhibitors, thapsigargin, and cyclopiazonic acid. However, the rise in [Na+]i produced by acetylcholine was not mimicked by thapsigargin or cyclopiazonic acid and was not prevented by previous depletion of Ca2+ pools. Depolarization of B-cells by acetylcholine stimulates Ca2+ influx and steadily increases [Ca2+]i. In the presence of glucose and extracellular Ca2+, B-cells treated with thapsigargin or cyclopiazonic acid displayed large [Ca2+]i oscillations. Subsequent application of acetylcholine was followed by a sustained rise in [Ca2+]i as in untreated cells. In conclusion, intracellular Ca2+ pool depletion does not mediate acetylcholine stimulation of Na+ entry and of subsequent events. We propose that the muscarinic receptors are coupled to Na+ channels in B-cells.
Miura
Y
Y
Unité d'Endocrinologie et Métabolisme, Faculty of Medicine, University of Louvain, Brussels, Belgium.
Gilon
P
P
Henquin
J C
JC
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D051379:Mice; D008815:Mice, Inbred Strains; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction; D012964:Sodium / Q000378:metabolism*; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin
D004791:Enzyme Inhibitors; D007211:Indoles; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic; D013729:Terpenes; D019284:Thapsigargin; D012964:Sodium; D000252:Calcium-Transporting ATPases; D005947:Glucose; D000109:Acetylcholine; D002118:Calcium; C000543:cyclopiazonic acid