Changes in osmolality modulate voltage-gated calcium channels in trigeminal ganglion neurons.
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).
Chen
Lei
L
Department of Physiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China. chenltj@htomail.com
Liu
Changjin
C
Liu
Lieju
L
D000818:Animals; D015220:Calcium Channels / Q000502:physiology*; D002478:Cells, Cultured; D003651:Decanoates / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006982:Hypertonic Solutions / Q000494:pharmacology; D007038:Hypotonic Solutions / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000235:genetics / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009994:Osmolar Concentration; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D050916:TRPV Cation Channels / Q000172:deficiency; D012668:Trigeminal Ganglion / Q000166:cytology*
D015220:Calcium Channels; D003651:Decanoates; D004791:Enzyme Inhibitors; D006982:Hypertonic Solutions; D007038:Hypotonic Solutions; D050916:TRPV Cation Channels; C486576:Trpv4 protein, mouse