Regulation of KCNQ1/KCNE1 by sphingomyelin synthase

2015 Fiscal Year Final Research Report

• Project/Area Number: 25670719
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Kumamoto University
• Principal Investigator: Wen-Jie Song 熊本大学, 生命科学研究部, 教授 (90216573)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: KCNQ1/KCNE1 / スフィンゴミエリン / PKD

Outline of Final Research Achievements

We previously showed that sphingomyelin synthase (SMS) deficiency leads to a reduction in expression of the K+ channel KCNQ1 in the inner ear, causing hearing loss. Here, we examined whether manipulation of SMS1 activity affects KCNQ1/KCNE1 currents in single cells. Application of tricyclodecan-9-ylxanthogenate, a nonspecific inhibitor of SMSs, significantly reduced current density and altered channel voltage dependence. Knockdown of SMS1 by a short hairpin RNA, however, reduced current density alone. Consistent with this, overexpression of SMS1 increased the current density without changing channel properties. Furthermore, application of protein kinase D inhibitors also suppressed current density without changing channel properties; this effect was nonadditive with that of SMS1 short hairpin RNA. These results suggest that SMS1 positively regulates KCNQ1/KCNE1 channel density in a protein kinase D-dependent manner.

Free Research Field

神経科学