Premium
Role of Voltage‐gated Ca 2+ Channels and Intracellular Ca 2+ in Rat Sympathetic Neuron Survival and Function Promoted by High K + and Cyclic AMP in the Presence or Absence of NGF
Author(s) -
Murrell Ruth D.,
Tolkovsky Aviva M.
Publication year - 1993
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.1993.tb00911.x
Subject(s) - cycloheximide , dihydropyridine , endocrinology , extracellular , medicine , neuron , channel blocker , nerve growth factor , nitrendipine , biology , calcium , intracellular , voltage dependent calcium channel , homeostasis , chemistry , biophysics , microbiology and biotechnology , neuroscience , biochemistry , protein biosynthesis , receptor
We have examined how NGF‐dependent rat sympathetic neurons maintain Ca 2+ 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 Ca 2+ channels within 2 days. Although resting [Ca 2+ ] i was elevated by 1.6‐fold, this was 50% less than the rise in [Ca 2+ ] i measured before down‐regulation occurred, suggesting that down‐regulation may help prevent the toxic effects of persistently elevated [Ca 2+ ] 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 Ca 2+ current, suggesting that voltage‐sensitive Ca 2+ 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 [Ca 2+ ] i , although neurites did not grow. Neither Ca 2+ channel density nor resting [Ca 2+ ] i were altered in neurons surviving with CPTcAMP. Moreover, CPTcAMP lowered the dependence on extracellular Ca 2+ . 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 [Ca 2+ ] i above resting levels to survive with either high K + or CPTcAMP, but dihydropyridine‐sensitive Ca 2+ channel activity may be essential for their survival promoting actions.