1. Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720, USA

Correspondence to: Mu-ming Poo¹ Correspondence and requests for materials should be addressed to M.P. (Email: mpoo@berkeley.edu).

Abstract

Ion channels formed by the TRP (transient receptor potential) superfamily of proteins act as sensors for temperature, osmolarity, mechanical stress and taste^{1, 2}. The growth cones of developing axons are responsible for sensing extracellular guidance factors, many of which trigger Ca²⁺ influx at the growth cone^{3, 4}; however, the identity of the ion channels involved remains to be clarified. Here, we report that TRP-like channel activity exists in the growth cones of cultured Xenopus neurons and can be modulated by exposure to netrin-1 and brain-derived neurotrophic factor, two chemoattractants for axon guidance. Whole-cell recording from growth cones showed that netrin-1 induced a membrane depolarization, part of which remained after all major voltage-dependent channels were blocked. Furthermore, the membrane depolarization was sensitive to blockers of TRP channels. Pharmacological blockade of putative TRP currents or downregulation of Xenopus TRP-1 (xTRPC1) expression with a specific morpholino oligonucleotide abolished the growth-cone turning and Ca²⁺ elevation induced by a netrin-1 gradient. Thus, TRPC currents reflect early events in the growth cone's detection of some extracellular guidance signals, resulting in membrane depolarization and cytoplasmic Ca²⁺ elevation that mediates the turning of growth cones.

1. Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720, USA

Correspondence to: Mu-ming Poo¹ Correspondence and requests for materials should be addressed to M.P. (Email: mpoo@berkeley.edu).

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.