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XB-ART-42120
J Neurosci September 29, 2010; 30 (39): 13192-200.

Induction of vertebrate regeneration by a transient sodium current.

Tseng AS , Beane WS , Lemire JM , Masi A , Levin M .


Abstract
Amphibians such as frogs can restore lost organs during development, including the lens and tail. To design biomedical therapies for organ repair, it is necessary to develop a detailed understanding of natural regeneration. Recently, ion transport has been implicated as a functional regulator of regeneration. Whereas voltage-gated sodium channels play a well known and important role in propagating action potentials in excitable cells, we have identified a novel role in regeneration for the ion transport function mediated by the voltage-gated sodium channel, Na(V)1.2. A local, early increase in intracellular sodium is required for initiating regeneration following Xenopus laevis tail amputation, and molecular and pharmacological inhibition of sodium transport causes regenerative failure. Na(V)1.2 is absent under nonregenerative conditions, but misexpression of human Na(V)1.5 can rescue regeneration during these states. Remarkably, pharmacological induction of a transient sodium current is capable of restoring regeneration even after the formation of a nonregenerative wound epithelium, confirming that it is the regulation of sodium transport that is critical for regeneration. Our studies reveal a previously undetected competency window in which cells retain their intrinsic regenerative program, identify a novel endogenous role for Na(V) in regeneration, and show that modulation of sodium transport represents an exciting new approach to organ repair.

PubMed ID: 20881138
PMC ID: PMC2965411
Article link: J Neurosci
Grant support: [+]

Species referenced: Xenopus
Genes referenced: hpse itih3 kcna2 kcna5 msx1 nav1 notch1 scn2a scn5a sik1 sik2 tbx2


Article Images: [+] show captions
References [+] :
Adams, H+ pump-dependent changes in membrane voltage are an early mechanism necessary and sufficient to induce Xenopus tail regeneration. 2007, Pubmed, Xenbase