GROWTH CONE NEUROTRANSMITTER RECEPTOR ACTIVATION MODULATES ELECTRIC FIELD-GUIDED NERVE GROWTH

We have studied the interactions between two nerve guidance cues, whic h alone induce substantial growth cone turning: endogenous neurotransm itters and small de electric fields. d-tubocurarine, a nicotinic AChR (acetylcholine receptor) antagonist, inhibited held-induced cathodal o rientation of cultured neurites, whereas atropine, a muscarinic AChR b locker, and suramin, a P-2-purinoceptor antagonist, markedly enhanced the guidance properties of the applied field. These experiments implic ate the activation of growth cone nicotinic AChRs by self-released ace tylcholine in the mechanism underpinning electric field-induced neurit e orientation and raise the possibility that growth cones release neur otransmitter prior to target interaction in order to assist their own pathfinding. Additionally, they provide the first evidence that coacti vation of several neurotransmitter receptors may interact to regulate directed nerve growth. Such interaction in vivo, where guidance signal s coexist, would add further levels of control to neurite guidance. (C ) 1995 Academic Press, Inc.