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  • Title: Massive exocytosis triggered by sodium-calcium exchange in sympathetic neurons is attenuated by co-culture with cardiac cells.
    Author: Wakade AR, Przywara DA, Bhave SV, Chowdhury PS, Bhave A, Wakade TD.
    Journal: Neuroscience; 1993 Aug; 55(3):813-21. PubMed ID: 8413937.
    Abstract:
    Entry of Ca2+ through voltage-dependent Ca2+ channels is known to be linked to the exocytotic release of transmitter from sympathetic neurons. In this paper we provide evidence that transmitter release can also be stimulated by Ca2+ influx via the Na-Ca exchanger. Furthermore, the release linked to Na-Ca exchange is regulated by cardiac target cells. Cultured sympathetic neurons of the chick embryo incubated in Ca2(+)-Mg(2+)-free Krebs solution for 20 min and then switched to Ca(2+)-containing solution exhibited 15-20-fold increases in [3H]noradrenaline release over the spontaneous release. Electrophysiologic studies showed that neurons were completely depolarized in Ca(2+)-Mg(2+)-free medium. Indo-1 fluorescence revealed a large and sustained increase in intracellular free Ca2+ concentration ([Ca2+]i) after addition of Ca2+ to Ca(2+)-Mg(2+)-free medium. The increased [3H]noradrenaline release and [Ca2+]i were dependent on external Na+ and Ca2+, but were not affected by the Ca2+ channel blockers lanthanum, cadmium, verapamil or omega-conotoxin. A conventional depolarizing stimulus (125 mM K+) produced a 13-fold increase in [3H]noradrenaline release over spontaneous release. However, K(+)-induced release and rise in [Ca2+]i declined rapidly and were sensitive to the Ca2+ channel blockers. When sympathetic neurons were co-cultured with embryonic cardiac cells the release induced by change from Ca(2+)-Mg(2+)-free to Ca(2+)-Krebs solution was dramatically reduced. The change from Ca(2+)-Mg(2+)-free to Ca(2+)-Krebs solution was ineffective in evoking [3H]noradrenaline release from sympathetic neurons in situ using perfused hearts of 15-day-old chick embryos.(ABSTRACT TRUNCATED AT 250 WORDS)
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