Involvement of dihydropyridine-sensitive calcium channels in nerve growth factor-dependent neurite outgrowth by sympathetic neurons.
We have used a number of pharmacological manipulations of calcium influx to alter the nerve growth factor (NGF)-elicited neurite outgrowth response of SCG neurons. Our results indicate that influx of extracellular calcium is critical to sympathetic SCG neurite outgrowth. Effective blockade of this process was produced by the inorganic calcium channel blockers Cd2+ (with an IC50 of 48 microM), Co2+ (129 microM), and Ni2+ (180 microM). More specifically, there is a significant contribution from dihydropyridine-sensitive L-type calcium channels to NGF-activated neurite outgrowth, as evidenced by the significant inhibition of neurite outgrowth by diltiazem (IC50 of 17 microM) and nifedipine (3 microM). Further, increases in calcium influx can elicit an enhanced neurite outgrowth response, as shown by the calcium channel agonist Bay K 8644 which potentiated neurite outgrowth by up to 40%.
Rogers
M
M
Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra.
Hendry
I
I
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004095:Dihydropyridines / Q000494:pharmacology*; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000187:drug effects; D008670:Metals / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D008670:Metals; D009414:Nerve Growth Factors