The nicotinic blocking agents d-tubocurare and alpha-bungarotoxin save motoneurons from naturally occurring death in the absence of neuromuscular blockade.
Motoneurons undergo a phase of target-dependent cell death during development. In chick embryos, motoneuronal death is blocked by the application of the nicotinic antagonists d-tubocurare (dTC) or alpha-bungarotoxin (alpha BTX). Paralytic doses of these drugs also increase intramuscular nerve branch formation. To investigate the possibility that a neuronal rather than a muscle-type nicotinic ACh receptor (nAChR) might be responsible for the toxin-induced arrest of naturally occurring motoneuronal death, we compared the doses of dTC and alpha-BTX required for paralysis with those needed to protect motoneurons from cell death. We also measured the effects of dTC on the survival of retrogradely labeled motoneurons in culture, and of various doses of dTC on intramuscular nerve branch formation. Subparalytic doses of dTC caused small but significant increases in nerve branch number, while higher doses produced larger effects. In contrast, motoneuronal survival was already maximal at doses of dTC or alpha-BTX below those needed for a visible effect on limb movement. Moreover, dTC increased motoneuron survival in culture, in the absence of muscle cells and muscle-type nAChRs. Nicotinic blocking agents can therefore rescue motoneurons with minimal depression of neuromuscular transmission, suggesting that this effect may be mediated through neuronal, rather than muscle-type.
D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002642:Chick Embryo; D009046:Motor Neurons / Q000187:drug effects*; D009132:Muscles / Q000294:innervation; D009424:Nervous System Physiological Phenomena; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology; D009538:Nicotine / Q000037:antagonists & inhibitors*; D014403:Tubocurarine / Q000494:pharmacology*
D002038:Bungarotoxins; D009466:Neuromuscular Blocking Agents; D009538:Nicotine; D014403:Tubocurarine