Histamine-induced intracellular free Ca++, inositol phosphates and electrical changes in murine N1E-115 neuroblastoma cells

S. G. Oakes, P. A. Iaizzo, E. Richelson, G. Powis

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Apparent intracellular free Ca++ concentration ([Ca++](i)) was measured in differentiated N1E-115 neuroblastoma by microinjecting cells with aequorin (estimated intracellular concentration, 4 μM) and measuring light emission. Histamine produced a transient, dose-dependent increase in [Ca++](i). Pyrilamine blocked completely the response to histamine whereas cimetidine had no effect. Omitting Ca++ from the external medium reversibly blocked the response. As well as a rise in [Ca++](i), histamine caused a concomitant cell hyperpolarization that was not blocked by ouabain, low Cl-, tetraethylammonium chloride/tetrodotoxin or metiamide but was blocked by apamin and pyrilamine. A secondary small depolarization caused by histamine was also blocked by apmin but not by ouabain, low Cl- or tetraethylammonium chloride/tetrodotoxin. Direct iontophoretic injection of Ca++ into cells caused only hyperpolarization. Injection of inositol 1,4,5-trisphosphate [IP3(1,4,5)] caused an increase in [Ca++](i) and rapid hyperpolarization. Inositol 1,3,4-trisphosphate [IP3(1,3,4)] caused an increase in [Ca++](i), rapid hyperpolarization and a slower depolarization. Repeated injections of IP3(1,3,4) led to a diminished [Ca++](i) response and decreased hyperpolarization but had no effect on depolarization. Inositol 1,3,4,5-tetrakisphosphate was without effect on [Ca++](i) or on cellular membrane potential. The results suggest that histamine causes an H1 receptor-dependent increase in [Ca++](i), probably by the increased entry of extracellular Ca++, although there may be a contribution from intracellular Ca++ released by IP3(1,4,5). The increase in [Ca++](i) activates K+ channels leading to cell hyperpolarization. IP3(1,3,4) formed from inositol 1,3,4,5-tetrakisphosphate, which is itself a product of IP3(1,4,5), causes a slower depolarization by a mechanism that does not involve Na+ channels or an increase in [Ca++](i).

Original languageEnglish (US)
Pages (from-to)114-121
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume247
Issue number1
StatePublished - 1988

ASJC Scopus subject areas

  • Pharmacology

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