Extracellular Hypotonicity Induces Disturbance Of Sodium Currents In Rat Ventricular Myocytes By PKC And Ca/CaMKⅡ

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 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. The results revealed that hypotonic solution reduced the amplitude of I_NaT and simultaneously augmented I_NaP with there being an interconversion between I_NaT and I_NaP. Hypotonic solution shifted steady-state inactivation to more negative potential, prolonged recovery time constant from inactivation, and enhanced intermediate inactivation (IIM) of voltage-dependent sodium channels. 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, but H-89 (inhibitor of PKA) and KT5823 (inhibitor of PKG) did not. Here we conclude that hypotonic solution inhibits I_NaT, enhances I_NaP and IIM with the effects being reversible. The intracellular Ca²⁺, PKC and Ca/CaMKII participate in the hypotonic modifications of sodium currents, but PKA and PKG do not.