A role for Na/Ca exchange in the pancreatic B cell. Studies with thapsigargin and caffeine

Sodium/calcium (Na/Ca) exchange is thought to play a role in Ca2+ extrusion from the pancreatic B cell. The aim of the present study was to provide direct evidence for such a role. The effect of extracellular Na+ (Na0+) removal on cytosolic free Ca2+ ([Ca2+]i) in single pancreatic B cells was examined using fura 2 and dual wavelength microfluorimetry. Isosmotical replacement of Na0+ by sucrose increased [Ca2+]i in the presence of extracellular Ca2+ but failed to affect [Ca2+]i in the absence of the divalent cation. Thapsigargin (1 microM), an inhibitor of the endoplasmic reticulum Ca(2+)-ATPase, induced a transient increase in [Ca2+]i in the presence of Na0+. This increase was enhanced and more sustained in the absence of Na0+. In the absence of Na0+ and the presence of thapsigargin, reintroduction of Na0+ induced a rapid decrease in [Ca2+]i. A similar picture was observed when caffeine (10 mM) was used to release Ca2+ from the endoplasmic reticulum. The decrease in [Ca2+]i induced by Na0+ reintroduction was accompanied by an important increase in 45Ca outflow from perifused islets. In conclusion, this study provides direct evidence that Na/Ca exchange may regulate B cell [Ca2+]i within physiological range.