The relationship between histamine-induced Ca2+ mobilization and Ca2+ entry in bovine adrenal chromaffin cells has been investigated. Stopped-flow fluorimetry of fura-2-loaded chromaffin cell populations revealed that 10 microM histamine promoted entry of Ca2+ or Mn2+ without measurable delay (< or = 20 ms), through a pathway that was insensitive to the dihydropyridine antagonist nifedipine. In the absence of extracellular Ca2+, or in the presence of 100 microM La3+, a blocker of receptor-mediated Ca2+ entry, 10 microM histamine triggered an elevation in intracellular calcium concentration ([Ca2+]i), but only after a delay of approx. 200 ms, which presumably represented the time required to mobilize intracellular Ca2+. These data suggested that histamine-induced bivalent-cation entry precedes extensive Ca2+ mobilization in chromaffin cells. In order to confirm that histamine can promote Ca2+ entry largely independently of mobilizing intracellular Ca2+, the ability of histamine to promote Ca2+ entry into cells whose intracellular Ca2+ store had been largely depleted was assessed. Fura-2-loaded chromaffin cells were treated with 10 microM ryanodine together with 40 mM caffeine, to deplete the hormone-sensitive Ca2+ store. This resulted in an approx. 95% inhibition of histamine-induced Ca2+ release. Under these conditions, histamine was still able to promote an entry of Ca2+ that was essentially indistinguishable from that promoted in control cells. In single cells, introduction of heparin (100 mg/ml), but not de-N-sulphated heparin (100 mg/ml), abolished the histamine-induced rise in [Ca2+]i. All these data suggest that histamine can induce G-protein- or inositol phosphate-dependent rapid (< or = 20 ms) Ca2+ entry without an extensive intracellular mobilization response in chromaffin cells, which points to activation of an entry mechanism distinct from the Ca(2+)-release-activated Ca2+ channel found in non-excitable cells.
Research Article|December 01 1994
Histamine-induced Ca2+ entry precedes Ca2+ mobilization in bovine adrenal chromaffin cells
T R Cheek;
M M Murawsky;
Biochem J (1994) 304 (2): 469-476.
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T R Cheek, M M Murawsky, K A Stauderman; Histamine-induced Ca2+ entry precedes Ca2+ mobilization in bovine adrenal chromaffin cells. Biochem J 1 December 1994; 304 (2): 469–476. doi: https://doi.org/10.1042/bj3040469
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