AJP - Endocrinology and Metabolism, Vol 271, Issue 3 E426-E433, Copyright © 1996 by American Physiological Society
No evidence for a role of reverse Na(+)-Ca2+ exchange in insulin release from mouse pancreatic islets
M. J. Garcia-Barrado, P. Gilon, Y. Sato, M. Nenquin and J. C. Henquin
Unite d'Endocrinologie et Metabolisme, University of Louvain School of Medicine, Brussels, Belgium.
We studied whether reverse Na(+)-Ca2+ exchange can increase cytoplasmic
Ca2+ ([Ca2+]i) in mouse islets and contribute to insulin release. The
exchange was stimulated by replacing Na+ with choline, sucrose, or lithium
in a medium containing 15 mM glucose. Na+ omission increased electrical
activity in B cells, [Ca2+]i, and insulin release. When voltage-dependent
Ca2+ channels were blocked by nimodipine or closed by holding the membrane
polarized with diazoxide, Na+ omission caused a slight hyperpolarization, a
small rise in [Ca2+]i, and a marginal increase in insulin release (the
latter only with choline). This small rise in [Ca2+]i was dependent on
extracellular Ca2+ but was hardly augmented when intracellular Na+ was
raised with alanine. When B cells were depolarized by 30 mM K+, Na+
omission did not affect the membrane potential but increased [Ca2+]i and
insulin release. If Ca2+ channels were blocked by nimodipine, only marginal
increases in Ca2+ and insulin release persisted, which were not different
from those observed when the cells were not depolarized. This indicates
that Ca2+ influx through voltage-dependent Ca2+ channels rather than via
reverse Na(+)-Ca2+ exchange underlies the rise in [Ca2+]i and in insulin
release produced by Na+ removal. No decisive support for Ca2+ influx by
reverse Na(+)-Ca2+ exchange could be found.
