Blockers of calcium permeability inhibit neurite extension and formation of neuromuscular synapses in cell culture.
Growth of neurites from trypsin-dissociated retinal neurons from chick embryos is very sensitive to the extracellular calcium concentration. Blockers of calcium permeability such as Co2+, Mn2+, La3+ and nitrendipine, when added to dissociated neurons, decrease the fraction of cells that extend neurites and the rate of neurite growth without influencing cell-substratum adhesion or survival capacity. Inhibition is concentration dependent, is related to the age of the donor chick embryo and can be prevented by increasing the extracellular calcium concentration. 50% inhibition in 8-day neurons is produced by 120 microM Co2+, 250 microM Mn2+, 50 microM La3+ and 10 microM nitrendipine in medium containing 1.8 mM Ca2+. Inhibition of neurite extension is accompanied by a concentration dependent inhibition of synapse formation between retinal neurons and muscle cells in culture, as determined by intracellular recording. 50% inhibition in the fraction of innervated myotubes is produced by 0.4 mM Co2+ and 4 mM Mn2+. These results suggest that: (1) a voltage-dependent calcium flux is a signal not only for growth cone expansion but also for neurite extension in primary dissociated neurons; and (2) that neurite extension is a prerequisite for synaptogenesis between neurons and muscle cells in culture.
D000367:Age Factors; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002642:Chick Embryo; D003035:Cobalt / Q000494:pharmacology; D005711:Gallopamil / Q000494:pharmacology; D007811:Lanthanum / Q000494:pharmacology; D008345:Manganese / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000187:drug effects*; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D009568:Nitrendipine; D012160:Retina / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002104:Cadmium; D005711:Gallopamil; D003035:Cobalt; D008345:Manganese; D007811:Lanthanum; D009568:Nitrendipine; D014700:Verapamil; D009543:Nifedipine