Dual role of calbindin-D28K in vesicular catecholamine release from mouse chromaffin cells.
Calbindin-D(28K) is suggested to play a postsynaptic role in neurotransmission and in the regulation of the intracellular Ca(2+) concentration. However, it is still unclear whether calbindin-D(28K) has a role in the regulation of exocytosis, either as Ca(2+) buffer or as Ca(2+) sensor. Amperometric recordings of catecholamine exocytosis from wild-type and calbindin-D(28K) knockout mouse chromaffin cells reveal a strong reduction in the number of released vesicles, as well as in the amount of neurotransmitter released per fusion event in knockout cells. However, Ca(2+) current recordings and Ca(2+) imaging experiments, including video-rate confocal laser scanning microscopy, revealed that the intracellular Ca(2+) dynamics are remarkably similar in wild-type and knockout cells. The combined results demonstrate that calbindin-D(28K) plays an important and dual role in exocytosis, affecting both release frequency and quantal size, apparently without strong effects on intracellular Ca(2+) dynamics. Consequently, the possibility that calbindin-D(28K) functions not only as a Ca(2+) buffer but also as a modulator of vesicular catecholamine release is discussed.
Westerink
R H S
RH
Cellular and Molecular Toxicology, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands. r.westerink@iras.uu.nl
Rook
M B
MB
Beekwilder
J P
JP
Wadman
W J
WJ
D000313:Adrenal Medulla / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D064092:Calbindin 1; D064026:Calbindins; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D002395:Catecholamines / Q000378:metabolism*; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000378:metabolism* / Q000648:ultrastructure; D022162:Cytoplasmic Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D005089:Exocytosis / Q000235:genetics; D005260:Female; D007150:Immunohistochemistry; D007424:Intracellular Fluid / Q000378:metabolism; D008297:Male; D008561:Membrane Fusion / Q000235:genetics; D008564:Membrane Potentials / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D064030:S100 Calcium Binding Protein G / Q000235:genetics / Q000502:physiology*; D009435:Synaptic Transmission / Q000235:genetics; D013572:Synaptic Vesicles / Q000378:metabolism / Q000648:ultrastructure
C576499:Calb1 protein, mouse; D064092:Calbindin 1; D064026:Calbindins; D002395:Catecholamines; D064030:S100 Calcium Binding Protein G; D002118:Calcium