Barium-induced exocytosis is due to internal calcium release and block of calcium efflux.
The concentration of cytosolic free Ca2+ ([Ca2+]i) and the release of tritiated norepinephrine ([3H]NE) were monitored during Ba2+ stimulation of sympathetic neurons cultured from chick embryos. Ba2+ (2.5 mM in Ca(2+)-free medium) caused a rise in [Ca2+]i in all regions (cell bodies, neurites, and growth cones) of sympathetic neurons and evoked [3H]NE release in the absence of other stimuli. The increase in [Ca2+]i and release of [3H]NE were sustained for up to 30 min in the presence of Ba2+. When Ba(2+)-stimulated cells were immediately washed in Ca(2+)-free Ba(2+)-free EGTA solution, both the elevated [Ca2+]i and [3H]NE release returned to basal levels, with similar, fast, time courses. Ba2+ also blocked Ca2+ efflux from neurons loaded with 45Ca. We conclude from the parallel effects of Ba2+ on [Ca2+]i and [3H]NE release that Ba2+ stimulates exocytosis by a Ca(2+)-dependent mechanism. The Ba(2+)-induced rise in [Ca2+]i is a result of two separate actions: (i) the release of Ca2+ from intracellular sites and (ii) an effective block of Ca2+ extrusion. The ability of Ba2+ to release Ca2+ in growth cones that are insensitive to caffeine suggests that Ba2+ may displace Ca2+ from binding sites other than endoplasmic reticulum.
Przywara
D A
DA
Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201.
Chowdhury
P S
PS
Bhave
S V
SV
Wakade
T D
TD
Wakade
A R
AR
D000818:Animals; D001464:Barium / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002642:Chick Embryo; D003600:Cytosol / Q000378:metabolism; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology*; D005456:Fluorescent Dyes / Q000378:metabolism; D005728:Ganglia, Sympathetic / Q000187:drug effects / Q000502:physiology*; D007091:Image Processing, Computer-Assisted; D007211:Indoles / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism
D005456:Fluorescent Dyes; D007211:Indoles; C059587:Indo-1 pentaacetoxymethyl ester; D001464:Barium; D002118:Calcium; D009638:Norepinephrine