Y. Miura et al., MUSCARINIC STIMULATION INCREASES NA-CELLS BY A MECHANISM OTHER THAN THE EMPTYING OF INTRACELLULAR CA2+ POOLS( ENTRY IN PANCREATIC B), Biochemical and biophysical research communications, 224(1), 1996, pp. 67-73
Stimulation of muscarinic (M(3)) receptors depolarizes pancreatic B-ce
lls 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 r
eceptors. Acetylcholine emptied Ca2+ pools less completely than did th
e SERCA pump inhibitors, thapsigargin, and cyclopiazonic acid. However
, the rise in [Na+](i) produced by acetylcholine was not mimicked by t
hapsigargin or cyclopiazonic acid and was not prevented by previous de
pletion of Ca2+ pools. Depolarization of B-cells by acetylcholine stim
ulates Ca2+ influx and steadily increases [Ca2+](i). In the presence o
f 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 de
pletion does not mediate acetylcholine stimulation of Na+ entry and of
subsequent events. We propose that the muscarinic receptors are coupl
ed to Na+ channels in B-cells. (C) 1996 Academic Press, Inc.