Role of voltage-gated Ca2+ channels and intracellular Ca2+ in rat sympathetic neuron survival and function promoted by high K+ and cyclic AMP in the presence or absence of NGF

Murrell, Ruth D and Tolkovsky, Aviva M (1993) Role of voltage-gated Ca2+ channels and intracellular Ca2+ in rat sympathetic neuron survival and function promoted by high K+ and cyclic AMP in the presence or absence of NGF. European Journal of Neuroscience, 5 (10). pp. 1261-1272. ISSN 0953-816X

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Abstract

We have examined how NGF-dependent rat sympathetic neurons maintain Ca2+ homeostasis when challenged with high K+ or 8-(4-chlorophenylthio)cyclic AMP (CPTcAMP), two survival factors. In the presence of NGF, high K+ (55 mM) caused a stable, 65% reduction in the density of cell soma voltage-sensitive Ca2+ channels within 2 days. Although resting [Ca2+]i was elevated by 1.6-fold, this was 50% less than the rise in [Ca2+]i measured before down-regulation occurred, suggesting that down-regulation may help prevent the toxic effects of persistently elevated [Ca2+]i. Inhibition of protein synthesis by cycloheximide blocked recovery from down-regulation. Moreover, treatment with cycloheximide or actinomycin-D caused a 2-fold rise in the peak Ca2+ current, suggesting that voltage-sensitive Ca2+ channel activity may be tonically attenuated during normal growth. In the absence of NGF, neurons survived for several days in high K+ medium with no significant rise in resting [Ca2+]i, although neurites did not grow. Neither Ca2+ channel density nor resting [Ca2+]i were altered in neurons surviving with CPTcAMP. Moreover, CPTcAMP lowered the dependence on extracellular Ca2+. However, the dihydropyridine antagonist nitrendipine blocked both high K(+)- and CPTcAMP-dependent survival although it had no effect in the presence of NGF. Thus, in the absence of NGF, sympathetic neurons do not require elevation of [Ca2+]i above resting levels to survive with either high K+ or CPTcAMP, but dihydropyridine-sensitive Ca2+ channel activity may be essential for their survival promoting actions.

Item Type: Article
Schools and Departments: School of Life Sciences > Biochemistry
Subjects: Q Science > QH Natural history > QH0301 Biology
Depositing User: Tom Gittoes
Date Deposited: 25 Mar 2015 10:54
Last Modified: 25 Mar 2015 10:54
URI: http://sro.sussex.ac.uk/id/eprint/52631
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