Intracellular calcium signaling induced by thapsigargin in excitable and inexcitable cells.
Signaling between intracellular Ca2+ stores and cell membrane channels or transporters is important to Ca(2+)-based second messenger systems. Two hypotheses, the capacitative and the Ca(2+)-induced Ca(2+)-influx models have been proposed to explain aspects of this signaling. In this study, we examined the applicability of these models in neuroendocrine (PC12), neuronal (dorsal root ganglion), immune (spleen), and fibroblast (3T3) cells. We used thapsigargin (TPG) to deplete specific intracellular Ca2+ stores and to increase the cytoplasmic Ca2+ concentration ([Ca2+]), and Ca2+ free medium to prevent Ca2+ influx and lower cytoplasmic [Ca2+]. We demonstrate that, although TPG causes an increase of [Ca2+]i in all cells examined, the subsequent stimulation of Ca2+ influx varies from high in spleen, to moderate in 3T3 and PC12, to undetectable in DRG cells. All cell types exhibited Ca2+ influx when Ca2+ was added to the medium following an exposure to Ca(2+)-free medium. Without added provisions, the two aforementioned hypotheses are inadequate in explaining the TPG-induced Ca(2+)-influx in all cell types. These results support the hypothesis of the existence of unique Ca2+ channels or transporters in spleen cells that operate subsequent to TPG treatment and are distinct from the voltage-gated Ca2+ channels and Ca(2+)-activated non-selective cation channels present in excitable cells.
Razani-Boroujerdi
S
S
Institute for Basic and Applied Research, Lovelace Institutes, Albuquerque, New Mexico.
Partridge
L D
LD
Sopori
M L
ML
D016475:3T3 Cells / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002451:Cell Compartmentation / Q000187:drug effects; D002642:Chick Embryo; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009928:Organ Specificity; D016716:PC12 Cells / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D015290:Second Messenger Systems / Q000187:drug effects*; D013154:Spleen / Q000166:cytology / Q000187:drug effects*; D013729:Terpenes / Q000494:pharmacology*; D019284:Thapsigargin
D013729:Terpenes; D019284:Thapsigargin; D000252:Calcium-Transporting ATPases; D002118:Calcium