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.
Herchuelz
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A
Laboratory of Pharmacology, Brussels University School of Medicine, Belgium.
Lebrun
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P
D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D005470:Fluorometry / Q000379:methods; D016257:Fura-2; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D013729:Terpenes / Q000494:pharmacology*; D019284:Thapsigargin
D013729:Terpenes; D002110:Caffeine; D019284:Thapsigargin; D012964:Sodium; D002118:Calcium; D016257:Fura-2