title: Acetylcholine elongates neuronal growth cone filopodia via activation of nicotinic acetylcholine receptors.
abstract: In addition to acting as a classical neurotransmitter in synaptic transmission, acetylcholine (ACh) has been shown to play a role in axonal growth and growth cone guidance. What is not well understood is how ACh acts on growth cones to affect growth cone filopodia, structures known to be important for neuronal pathfinding. We addressed this question using an identified neuron (B5) from the buccal ganglion of the pond snail Helisoma trivolvis in cell culture. ACh treatment caused pronounced filopodial elongation within minutes, an effect that required calcium influx and resulted in the elevation of the intracellular calcium concentration ([Ca]i ). Whole-cell patch clamp recordings showed that ACh caused a reduction in input resistance, a depolarization of the membrane potential, and an increase in firing frequency in B5 neurons. These effects were mediated via the activation of nicotinic acetylcholine receptors (nAChRs), as the nAChR agonist dimethylphenylpiperazinium (DMPP) mimicked the effects of ACh on filopodial elongation, [Ca]i elevation, and changes in electrical activity. Moreover, the nAChR antagonist tubucurarine blocked all DMPP-induced effects. Lastly, ACh acted locally at the growth cone, because growth cones that were physically isolated from their parent neuron responded to ACh by filopodial elongation with a similar time course as growth cones that remained connected to their parent neuron. Our data revealed a critical role for ACh as a modulator of growth cone filopodial dynamics. ACh signaling was mediated via nAChRs and resulted in Ca influx, which, in turn, caused filopodial elongation.
authors: Biology Department, Georgia State University, Atlanta, GA 30302, USA.
authors: Lei Ray
authors: LR
authors: Zhong
authors: Stephen
authors: S
authors: Estes
authors: Liana
authors: L
authors: Artinian
authors: Vincent
authors: V
authors: Rehder
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D020439:Growth Cones / Q000187:drug effects / Q000502:physiology*; D006372:Helix, Snails; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D011554:Pseudopodia / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D011978:Receptors, Nicotinic / Q000378:metabolism* / Q000502:physiology
chemical_list: D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D004246:Dimethylphenylpiperazinium Iodide; D000109:Acetylcholine