Regulation of membrane KCNQ1/KCNE1 channel density by sphingomyelin synthase 1.
Am J Physiol Cell Physiol
; 311(1): C15-23, 2016 07 01.
Article
em En
| MEDLINE
| ID: mdl-27194473
ABSTRACT
Sphingomyelin synthase (SMS) catalyzes the conversion of phosphatidylcholine and ceramide to sphingomyelin and diacylglycerol. We previously showed that SMS1 deficiency leads to a reduction in expression of the K(+) channel KCNQ1 in the inner ear (Lu MH, Takemoto M, Watanabe K, Luo H, Nishimura M, Yano M, Tomimoto H, Okazaki T, Oike Y, and Song WJ. J Physiol 590 4029-4044, 2012), causing hearing loss. However, it remains unknown whether this change in expression is attributable to a cellular process or a systemic effect in the knockout animal. Here, we examined whether manipulation of SMS1 activity affects KCNQ1/KCNE1 currents in individual cells. To this end, we expressed the KCNQ1/KCNE1 channel in human embryonic kidney 293T cells and evaluated the effect of SMS1 manipulations on the channel using whole cell recording. Application of tricyclodecan-9-yl-xanthogenate, 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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Potássio
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Membrana Celular
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Transferases (Outros Grupos de Fosfato Substituídos)
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Canais de Potássio de Abertura Dependente da Tensão da Membrana
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Canal de Potássio KCNQ1
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Proteínas de Membrana
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Proteínas do Tecido Nervoso
Limite:
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article