Muscarinic stimulation increases Na+ entry in pancreatic B-cells by a mechanism other than the emptying of intracellular Ca2+ pools

Biochem Biophys Res Commun. 1996 Jul 5;224(1):67-73. doi: 10.1006/bbrc.1996.0985.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology*
  • Animals
  • Calcium / metabolism*
  • Calcium-Transporting ATPases / antagonists & inhibitors
  • Cells, Cultured
  • Enzyme Inhibitors / pharmacology
  • Female
  • Glucose / pharmacology
  • Indoles / pharmacology
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / physiology*
  • Kinetics
  • Mice
  • Mice, Inbred Strains
  • Receptor, Muscarinic M3
  • Receptors, Muscarinic / drug effects
  • Receptors, Muscarinic / physiology*
  • Signal Transduction
  • Sodium / metabolism*
  • Terpenes / pharmacology
  • Thapsigargin

Substances

  • Enzyme Inhibitors
  • Indoles
  • Receptor, Muscarinic M3
  • Receptors, Muscarinic
  • Terpenes
  • Thapsigargin
  • Sodium
  • Calcium-Transporting ATPases
  • Glucose
  • Acetylcholine
  • Calcium
  • cyclopiazonic acid