PMID- 19428701 OWN - NLM STAT- MEDLINE DCOM- 20090721 LR - 20220410 IS - 1872-8111 (Electronic) IS - 0168-0102 (Print) IS - 0168-0102 (Linking) VI - 64 IP - 2 DP - 2009 Jun TI - Changes in osmolality modulate voltage-gated sodium channels in trigeminal ganglion neurons. PG - 199-207 LID - 10.1016/j.neures.2009.02.012 [doi] AB - 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. FAU - Chen, Lei AU - Chen L AD - Department of Physiology, Tongji Medical College, Huazhong University of Science and Technology, No. 13, Hangkong Road, Wuhan 430030, PR China. FAU - Liu, Changjin AU - Liu C FAU - Liu, Lieju AU - Liu L FAU - Cao, Xuehong AU - Cao X LA - eng GR - R01 GM063577/GM/NIGMS NIH HHS/United States GR - R01 GM063577-04/GM/NIGMS NIH HHS/United States GR - GM-63577/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20090313 PL - Ireland TA - Neurosci Res JT - Neuroscience research JID - 8500749 RN - 0 (Hypertonic Solutions) RN - 0 (Hypotonic Solutions) RN - 0 (Isotonic Solutions) RN - 0 (Sodium Channels) RN - 0 (TRPV Cation Channels) RN - 0 (Trpv4 protein, mouse) RN - 0 (Trpv4 protein, rat) RN - 4368-28-9 (Tetrodotoxin) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases) RN - EC 2.7.11.12 (Cyclic GMP-Dependent Protein Kinases) RN - EC 2.7.11.13 (Protein Kinase C) RN - EC 3.1.4.- (Type C Phospholipases) SB - IM MH - Animals MH - Cells, Cultured MH - Cyclic AMP-Dependent Protein Kinases/physiology MH - Cyclic GMP-Dependent Protein Kinases/physiology MH - Hypertonic Solutions MH - Hypotonic Solutions MH - Ion Channel Gating MH - Isotonic Solutions MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Neurons/*physiology MH - Osmolar Concentration MH - Phosphatidylinositol 3-Kinases/physiology MH - Protein Kinase C/physiology MH - Rats MH - Rats, Sprague-Dawley MH - Sodium Channels/*physiology MH - TRPV Cation Channels/agonists/antagonists & inhibitors/genetics/physiology MH - Tetrodotoxin/pharmacology MH - Trigeminal Ganglion/cytology/*physiology MH - Type C Phospholipases/physiology PMC - PMC2684961 MID - NIHMS102852 EDAT- 2009/05/12 09:00 MHDA- 2009/07/22 09:00 PMCR- 2010/06/01 CRDT- 2009/05/12 09:00 PHST- 2008/11/09 00:00 [received] PHST- 2009/01/24 00:00 [revised] PHST- 2009/02/26 00:00 [accepted] PHST- 2009/05/12 09:00 [entrez] PHST- 2009/05/12 09:00 [pubmed] PHST- 2009/07/22 09:00 [medline] PHST- 2010/06/01 00:00 [pmc-release] AID - S0168-0102(09)00081-9 [pii] AID - 10.1016/j.neures.2009.02.012 [doi] PST - ppublish SO - Neurosci Res. 2009 Jun;64(2):199-207. doi: 10.1016/j.neures.2009.02.012. Epub 2009 Mar 13.