Changes in osmolality modulate voltage-gated calcium channels in trigeminal ganglion neurons

Brain Res. 2008 May 7;1208:56-66. doi: 10.1016/j.brainres.2008.02.048. Epub 2008 Feb 29.


Voltage-gated calcium channels (VGCCs) participate in many important physiological functions. However whether VGCCs are modulated by changes of osmolarity and involved in anisotonicity-induced nociception is still unknown. For this reason by using whole-cell patch clamp techniques in rat and mouse trigeminal ganglion (TG) neurons we tested the effects of hypo- and hypertonicity on VGCCs. We found that high-voltage-gated calcium current (I(HVA)) was inhibited by both hypo- and hypertonicity. In rat TG neurons, the inhibition by hypotonicity was mimicked by Transient Receptor Potential Vanilloid 4 receptor (TRPV4) activator but hypotonicity did not exhibit inhibition in TRPV4(-/-) mice TG neurons. Concerning the downstream signaling pathways, antagonism of PKG pathway selectively reduced the hypotonicity-induced inhibition, whereas inhibition of PLC- and PI3K-mediated pathways selectively reduced the inhibition produced by hypertonicity. In summary, although the effects of hypo- and hypertonicity show similar phenotype, receptor and intracellular signaling pathways were selective for hypo- versus hypertonicity-induced inhibition of I(HVA).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channels / physiology*
  • Cells, Cultured
  • Decanoates / pharmacology
  • Dose-Response Relationship, Radiation
  • Electric Stimulation / methods
  • Enzyme Inhibitors / pharmacology
  • Hypertonic Solutions / pharmacology
  • Hypotonic Solutions / pharmacology
  • Male
  • Membrane Potentials / genetics
  • Membrane Potentials / radiation effects
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurons / drug effects
  • Neurons / physiology*
  • Osmolar Concentration
  • Patch-Clamp Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Signal Transduction / radiation effects
  • TRPV Cation Channels / deficiency
  • Trigeminal Ganglion / cytology*


  • Calcium Channels
  • Decanoates
  • Enzyme Inhibitors
  • Hypertonic Solutions
  • Hypotonic Solutions
  • TRPV Cation Channels
  • Trpv4 protein, mouse