Cardio-Electrophysiological Research Laboratory, Medical College, Wuhan University of Science and Technology, Wuhan, China.
Physiol Res. 2009;58(6):807-815. doi: 10.33549/physiolres.931692. Epub 2008 Dec 17.
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.
低渗溶液会改变离子通道的活性，但人们对电压依赖性钠通道的关注较少。本研究旨在探讨低渗溶液对瞬时钠电流（I(NaT)）和持续钠电流（I(NaP)）的影响。我们还探讨了细胞内信号转导系统是否参与了钠电流的低渗修饰。通过全细胞膜片钳技术在分离的大鼠心室肌细胞中记录 I(NaT)和 I(NaP)。我们的结果表明，低渗溶液降低了 I(NaT)，同时增加了 I(NaP)，同时 I(NaT)和 I(NaP)之间发生了转换。低渗溶液将稳态失活向更负的电位移动，延长了失活恢复时间，并增强了中间失活（I(IM)）。钌红（RR，TRPV4 抑制剂）、双吲哚基马来酰亚胺 VI（BIM，PKC 抑制剂）、Kn-93（Ca/CaMKII 抑制剂）和 BAPTA（Ca(2+)-螯合剂）抑制了低渗溶液对 I(NaT)和 I(NaP)的作用。因此，我们得出结论，低渗溶液抑制 I(NaT)，增强 I(NaP)和 I(IM)，其作用是可逆的。TRPV4 和细胞内 Ca(2+)、PKC 和 Ca/CaMKII 参与了钠电流的低渗修饰。
