Histamine-induced calcium entry in rat cerebellar astrocytes: evidence for capacitative and non-capacitative mechanisms.
We have investigated the effects of histamine on the intracellular calcium concentration ([Ca2+]i) of cultured rat cerebellar astrocytes using fura-2-based Ca2+ imaging microscopy. Most of the cells responded to the application of histamine with an increase in [Ca2+]i which was antagonized by the H1 receptor blocker mepyramine. When histamine was applied for several minutes, the majority of the cells displayed a biphasic Ca2+ response consisting of an initial transient peak and a sustained component. In contrast to the initial transient [Ca2+]i response, the sustained, receptor-activated increase in [Ca2+]i was rapidly abolished by chelation of extracellular Ca2+ or addition of Ni2+, Mn2+, Co2+ and Zn2+, but was unaffected by nifedipine, an antagonist of L-type voltage-activated Ca2+ channels. These data indicate that the sustained increase in [Ca2+]i was dependent on Ca2+ influx. When intracellular Ca2+ stores were emptied by prolonged application of histamine in Ca2+-free conditions, Ca2+ re-addition after removal of the agonist did not lead to an 'overshoot' of [Ca2+]i indicative of store-operated Ca2+ influx. However, Ca2+ stores were refilled despite the absence of any substantial change in the fura-2 signal. Depletion of intracellular Ca2+ stores using cyclopiazonic acid in Ca2+-free saline and subsequent re-addition of Ca2+ to the saline resulted in an increase in [Ca2+]i that was significantly enhanced in the presence of histamine. The results suggest that besides capacitative mechanisms, a non-capacitative, voltage-independent pathway is involved in histamine-induced Ca2+ entry into cultured rat cerebellar astrocytes.
Jung
S
S
Abteilung fur Allgemeine Zoologie, FB Biologie, Universitat Kaiserslautern, Postfach 3049, D-67653 Kaiserslautern, Germany.
Pfeiffer
F
F
Deitmer
J W
JW
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D004594:Electrophysiology; D005456:Fluorescent Dyes; D016257:Fura-2; D006632:Histamine / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D008670:Metals / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002614:Chelating Agents; D005456:Fluorescent Dyes; D006634:Histamine H1 Antagonists; D008670:Metals; D006632:Histamine; D011738:Pyrilamine; D009543:Nifedipine; D002118:Calcium; D016257:Fura-2