title: Extracellular hypotonicity induces disturbance of sodium currents in rat ventricular myocytes.
abstract: Hypotonic solution alters ion channel activity, but little attention has been paid to voltage-dependent sodium channels. The aim of this study was to investigate the effects of hypotonic solution on transient sodium currents (I(NaT)) and persistent sodium currents (I(NaP)). We also explored whether the intracellular signal transduction systems participated in the hypotonic modifications of sodium currents. I(NaT) and I(NaP) were recorded by means of whole-cell patch-clamp technique in isolated rat ventricular myocytes. Our results revealed that hypotonic solution reduced I(NaT) and simultaneously augmented I(NaP) with the occurrence of interconversion between I(NaT) and I(NaP). Hypotonic solution shifted steady-state inactivation to a more negative potential, prolonged the time of recovery from inactivation, and enhanced intermediate inactivation (I(IM)). Ruthenium red (RR, inhibitor of TRPV4), bisindolylmaleimide VI (BIM, inhibitor of PKC), Kn-93 (inhibitor of Ca/CaMKII) and BAPTA (Ca(2+)-chelator) inhibited the effects of hypotonic solution on I(NaT) and I(NaP). Therefore we conclude that hypotonic solution inhibits I(NaT), enhances I(NaP) and I(IM) with the effects being reversible. TRPV4 and intracellular Ca(2+), PKC and Ca/CaMKII participate in the hypotonic modifications of sodium currents.
authors.affiliation: Cardio-Electrophysiological Research Laboratory, Medical College, Wuhan University of Science and Technology, Wuhan, China. mjhua@wust.edu.cn
authors.forename: L
authors.initials: L
authors.lastname: Hu
authors.forename: J
authors.initials: J
authors.lastname: Ma
authors.forename: P
authors.initials: P
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Zheng
mesh_terms: D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007038:Hypotonic Solutions; D007211:Indoles / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D008564:Membrane Potentials; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D012430:Ruthenium Red / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D012964:Sodium / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D000096926:Benzenesulfonamides
chemical_list: D001596:Benzylamines; D002118:Calcium; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002614:Chelating Agents; D004533:Egtazic Acid; D007038:Hypotonic Solutions; D007211:Indoles; D008301:Maleimides; D011493:Protein Kinase C; D047428:Protein Kinase Inhibitors; D012430:Ruthenium Red; D012964:Sodium; D013449:Sulfonamides; D050916:TRPV Cation Channels; C486577:Trpv4 protein, rat; C072105:KN 93; D000096926:Benzenesulfonamides; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; C088060:bisindolylmaleimide