Extracellular Hypotonicity Induces Disturbance of Sodium Currents in Rat Ventricular Myocytes

摘要

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 (Ca2+-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 Ca2+, PKC and Ca/CaMKII participate in the hypotonic modifications of sodium currents.