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Sci. STKE, 22 October 2002
Vol. 2002, Issue 155, p. tw385
[DOI: 10.1126/stke.2002.155.tw385]


Sodium Channels Neurotrophin Depolarization

Neurotrophins are best known for their role in neuron survival and differentiation, effects that are mediated by kinase cascades activated by receptor tyrosine kinases. Brain-derived neurotrophic factor (BDNF) is also able to stimulate rapid depolarization through the activation of a Na+ current (INa). Blum et al. identified a saxitoxin (STX)-sensitive, tetrodotoxin (TTX)-insensitive INa that was stimulated by BDNF in both cultured hippocampal neurons and differentiated SH-SY5Y cells. They used antisense RNA to inhibit the expression of the TrkB receptor and the voltage-gated sodium channel Nav1.9 (predicted to be STX-sensitive, TTX-insensitive on the basis of its amino acid sequence) in SH-SY5Y neuroblastoma cells. Inhibition of TrkB or Nav1.9 resulted in the complete loss of BDNF-stimulated INa. Antisense treatment for TrkC or a TTX-sensitive Na+ channel had no effect, even though these two genes were expressed in the SH-SY5Y cells. BDNF-stimulated INa was reconstituted in human embryonic kidney (HEK) 293 cells by coexpression of Nav1.9 and TrkB, These results suggest that a voltage-gated ion channel may be also ligand activated. Presumably, TrkB can associate directly or indirectly with the sodium channel to transmit the growth factor signal to the channel. Barde discusses the implications of these results for pain perception and the possibility that similar interactions may occur between other neurotrophins, their receptors, and voltage-gated ion channels.

R. Blum, K. W. Kafitz, A. Konnerth, Neurotrophin-evoked depolarization requires the sodium channel Nav1.9. Nature 419, 687-693 (2002). [Online Journal]

Y.A. Barde, Neurotrophin channels excitement. Nature 419, 683-684 (2002). [Online Journal]

Citation: Neurotrophin Depolarization. Sci. STKE 2002, tw385 (2002).

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