K(+) efflux through two-pore domain K(+) channels is required for mouse embryonic development
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Published on: January 12, 2015
Chang-Gi Hur1, Eun-Jin Kim, Seong-Keun Cho
1Department of Physiology, Institute of Health Sciences, Gyeongsang National University School of Medicine, 90 Chilam, Jinju 660-751, South Korea.
Abstract:
Numerous studies have suggested that K(+) channels regulate a wide range of physiological processes in mammalian cells. However, little is known about the specific function of K(+) channels in germ cells. In this study, mouse zygotes were cultured in a medium containing K(+) channel blockers to identify the functional role of K(+) channels in mouse embryonic development. Voltage-dependent K(+) channel blockers, such as tetraethylammonium and BaCl(2), had no effect on embryonic development to the blastocyst stage, whereas K(2P) channel blockers, such as quinine, selective serotonin reuptake inhibitors (fluoxetine, paroxetine, and citalopram), gadolinium trichloride, anandamide, ruthenium red, and zinc chloride, significantly decreased blastocyst formation (P<0.05). RT-PCR data showed that members of the K(2P) channel family, specifically KCNK2, KCNK10, KCNK4, KCNK3, and KCNK9, were expressed in mouse oocytes and embryos. In addition, their mRNA expression levels, except Kcnk3, were up-regulated by above ninefold in morula-stage embryos compared with 2-cell stage embryos (2-cells). Immunocytochemical data showed that KCNK2, KCNK10, KCNK4, KCNK3, and KCNK9 channel proteins were expressed in the membrane of oocytes, 2-cells, and blastocysts. Each siRNA injection targeted at Kcnk2, Kcnk10, Kcnk4, Kcnk3, and Kcnk9 significantly decreased blastocyst formation by ~38% compared with scrambled siRNA injection (P<0.05). The blockade of K(2P) channels acidified the intracellular pH and depolarized the membrane potential. These results suggest that K(2P) channels could improve mouse embryonic development through the modulation of gating by activators.
Insights
Potassium (K+) channels, specifically K2P channels, are crucial for mouse embryonic development. Blocking these channels impairs blastocyst formation by altering intracellular pH and membrane potential.
Area of Science:
- Cell Biology
- Developmental Biology
- Physiology
Background:
- Potassium (K+) channels are vital for numerous physiological processes in mammalian cells.
- The specific role of K+ channels in germ cells and early embryonic development remains largely unexplored.
Purpose of the Study:
- To investigate the functional significance of K+ channels in mouse embryonic development.
- To identify specific K+ channel subtypes involved in early mouse embryogenesis.
Main Methods:
- Mouse zygotes were cultured with various K+ channel blockers.
- Gene expression analysis using RT-PCR identified K2P channel family members (KCNK2, KCNK10, KCNK4, KCNK3, KCNK9) in oocytes and embryos.
- Immunocytochemistry confirmed the protein expression of these channels.
- siRNA-mediated gene silencing was employed to assess the impact of specific K2P channels on development.
Main Results:
- K2P channel blockers significantly reduced blastocyst formation, unlike voltage-dependent K+ channel blockers.
- mRNA expression of KCNK2, KCNK10, KCNK4, and KCNK9 was significantly upregulated from the 2-cell to morula stage.
- siRNA targeting of Kcnk2, Kcnk10, Kcnk4, Kcnk3, and Kcnk9 individually decreased blastocyst formation by approximately 38%.
- K2P channel blockade led to intracellular acidification and membrane depolarization.
Conclusions:
- K2P channels play a critical role in supporting mouse embryonic development to the blastocyst stage.
- These channels appear to influence development by modulating intracellular pH and membrane potential.
- K2P channel activity is essential for successful early embryogenesis in mice.
