ZFIN ID: ZDB-PUB-080922-15
Sensory neuron sodium current requires nongenomic actions of thyroid hormone during development
Yonkers, M.A., and Ribera, A.B.
Date: 2008
Source: Journal of neurophysiology   100(5): 2719-2725 (Journal)
Registered Authors: Ribera, Angie, Yonkers, Marc
Keywords: none
MeSH Terms:
  • Animals
  • Antibodies, Monoclonal/pharmacology
  • Dose-Response Relationship, Radiation
  • Drug Interactions
  • Electric Stimulation/methods
  • Embryo, Nonmammalian
  • In Vitro Techniques
  • Integrin alphaVbeta3/antagonists & inhibitors
  • Models, Biological
  • Patch-Clamp Techniques
  • Sensory Receptor Cells/drug effects*
  • Sensory Receptor Cells/radiation effects
  • Sodium Channels/physiology*
  • Spinal Cord/cytology
  • Spinal Cord/embryology
  • Thyroid Hormones/metabolism
  • Thyroid Hormones/pharmacology*
  • Thyroxine/analogs & derivatives
  • Thyroxine/pharmacology
  • Time Factors
  • Touch
  • Zebrafish
PubMed: 18799597 Full text @ J. Neurophysiol.
To identify embryonic roles for thyroid hormone we tested for effects on a key neuronal trait, voltage-gated sodium current (INa) in the zebrafish model system. We recorded from Rohon-Beard sensory neurons (RBs) using whole cell voltage-clamp methods. Here, we provide evidence for regulation of INa by thyroid hormone in vivo. Chronic application of thyroid hormone increased RB peak INa density 1.4-fold. However, an acute 5 minute application sufficed to increase INa density to the same extent, a time course not expected for a genomic mechanism. A thyroid hormone blocker, tetrac, blocked both chronic and acute effects. Further, the thyroid hormone precursor thyroxine (T4) affected INa, yet the traditionally active form triiodothyronine (T3) did not. Consequently, we tested for a nonconventional T4 receptor. LM609, a selective antagonist of the alphaVbeta3 integrin, occluded the rapid effect of T4, implicating a specific integrin dimer as a T4 receptor. Chronic application of either tetrac or LM609 reduced sodium conductance significantly, demonstrating an in vivo requirement for T4-integrin regulation of INa. Further, reducing endogenous T4 levels via yolkectomy reduced sodium conductance, an effect that was partially rescued by T4 supplementation following surgery. Because RBs mediate the embryonic touch response, we also tested for behavioral effects. Tetrac and LM609 significantly reduced the percent of touch trials eliciting a normal touch response. T4's rapid effect on RB INa highlights the importance of T4 availability and nongenomic T4 signaling during embryogenesis.