Changes in osmolality modulate voltage-gated sodium channels in trigeminal ganglion neurons.
Voltage-gated sodium channels (VGSCs) are important channels which participate in many physiological functions. Whether VGSCs can be modulated by changes in osmolality in trigeminal ganglion (TG) neurons remains unknown. In this study, by using whole-cell patch clamp techniques, we tested the effects of hypo- and hypertonicity on VGSCs in cultured TG neurons. Our data show that tetrodotoxin-resistant sodium current (TTX-R current) was inhibited in the presence of hypo- and hypertonic solutions. In hypertonic solutions both voltage-dependent activation and inactivation curves shifted to the hyperpolarizing direction, while in hypotonic solutions only inactivation curve shifted to the hyperpolarizing direction. Transient Receptor Potential Vanilloid 4 (TRPV4) receptor activator mimicked the inhibition of TTX-R current by hypotonicity and the inhibition by hypotonicity was markedly attenuated by TRPV4 receptor blocker and in TRPV4(-/-) mice TG neurons. We also demonstrate that the inhibition of PKA selectively attenuated hypotonicity-induced inhibition, whereas antagonism of PLC and PI3K selectively attenuated hypertonicity-induced inhibition. We conclude that although hypo- and hypertonicity have similar effect on VGSCs, receptor and intracellular signaling pathways are different for hypo- versus hypertonicity-induced inhibition of TTX-R current.
Department of Physiology, Tongji Medical College, Huazhong University of Science and Technology, No. 13, Hangkong Road, Wuhan 430030, PR China.
Lei
L
Chen
Changjin
C
Liu
Lieju
L
Liu
Xuehong
X
Cao
D000818:Animals; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000502:physiology; D006982:Hypertonic Solutions; D007038:Hypotonic Solutions; D015640:Ion Channel Gating; D007552:Isotonic Solutions; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology*; D009994:Osmolar Concentration; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000502:physiology*; D050916:TRPV Cation Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D012668:Trigeminal Ganglion / Q000166:cytology / Q000502:physiology*; D010738:Type C Phospholipases / Q000502:physiology
D006982:Hypertonic Solutions; D007038:Hypotonic Solutions; D007552:Isotonic Solutions; D015222:Sodium Channels; D050916:TRPV Cation Channels; C486576:Trpv4 protein, mouse; C486577:Trpv4 protein, rat; D013779:Tetrodotoxin; D019869:Phosphatidylinositol 3-Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D011493:Protein Kinase C; D010738:Type C Phospholipases