Histamine-induced Ca2+ release in bovine adrenal chromaffin cells.
The histamine-induced biphasic increase of the intracellular free [Ca2+] ([Ca2+]i) was studied in bovine adrenal chromaffin cells using fura-2 microfluorimetry and the whole-cell patch-clamp technique. Both the rapid, transient Ca2+ rise and the sustained plateau component of elevated [Ca2+]i were independent of extracellular Ca2+. Incubation with the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) blocker thapsigargin diminished histamine-induced changes in [Ca2+]i. When Ca2+ release was either stimulated by IP3 or blocked with the competitive inhibitor heparin, histamine was unable to elicit the typical Ca2+ rise. Ryanodine, tetracaine and ruthenium red, all blockers of Ca2+ release from caffeine-sensitive stores, had only minor effects on the agonist-induced Ca2+ changes. The contribution of mitochondria in shaping the histamine-induced Ca2+ increase was studied using ruthenium red and the two proton ionophores carbonylcyanide m-chlorophenylhydrazone (CCCP) and carbonylcyanide p-(trifluoromethoxy)phenylhydrazone (FCCP). Both mitochondrial uncouplers reversibly increased [Ca2+]i and induced an inward current leading to cell membrane depolarisation. In summary, these results indicate that Ca2+ from IP3-sensitive stores is essential for the generation of both the transient increase and secondary elevation in [Ca2+]i.
Bödding
M
M
Abteilung für Membranbiophysik, Max-Planck-Institut für biophysikalische Chemie, Göttingen, Germany. matthias.boedding@med-rz.uni-sb.de
D000313:Adrenal Medulla / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004533:Egtazic Acid / Q000494:pharmacology; D004558:Electric Stimulation; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D006632:Histamine / Q000378:metabolism*; D017442:Histamine Agonists / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D019284:Thapsigargin / Q000494:pharmacology
D017442:Histamine Agonists; D006633:Histamine Antagonists; D002110:Caffeine; D004533:Egtazic Acid; D019284:Thapsigargin; D006632:Histamine; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium