Volume-related ion channels involved in cell survival-death switching Текст научной статьи по специальности «Биологические науки»

Abstracts

VOLUME-RELATED ION CHANNELS INVOLVED IN CELL SURVIVAL-DEATH SWITCHING

Okada, Y.1, Sato-Numata, K.1, Numata, T.1, Wehner, F.2, Shimizu, T.3, Sakai, H.3, Akita, T.1, and Okada, T.1

'National Institute for Physiological Science, Okazaki, Japan 2Max-Planck-Institute of Molecular Physiology, Dortmund, Germany

3Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan

Cell volume regulation is essential for survival of animal cells. The regulatory volume decrease (RVD) and increase (RVI) are accomplished by water movement driven by KCl efflux and NaCl influx, respectively, mediated by a number of Cl-, K+ and cation channels. Persistent cell shrinkage and swelling are major hallmarks of apoptotic and necrotic cell death, respectively, and caused by the apoptotic volume decrease (AVD) and necrotic volume increase (NVI) coupled to impairment of RVI and RVD, respectively. Since the AVD and NVI processes also involve activities of Cl-, K+ and cation channels, it is likely that these volume-related ion channels (such as volume-sensitive outwardly rectifying anion channel (VSOR), CFTR, hypertonicity-induced cation channel (HICC), acid-sensitive outwardly rectifying anion channel (ASOR) and TRPM7) play roles in the cell survival-death switching. In fact, our studies in vitro showed that apop-totic and necrotic cell death is induced or rescued by controlling activities of these volume-related ion channels under a variety of conditions, including apoptotic stimula-

tion, excitotoxicity, acidotoxicity, lactacidosis and hypox-ia-reoxygenation. Also, ischemia-reperfusion-induced neuronal apoptosis and cardiac necrosis in vivo were found to be rescued by controlling volume-related anion channel activities. Among these volume-related ion channels, the molecular entities of VSOR and ASOR remain elusive. Although TMEM16F (ANO6) and ClC-3 were proposed as the molecular candidates for VSOR and ASOR, respectively, our recent studies excluded these possibilities and showed that they function as distinct-typed Ca2+-activated and outwardly rectifying chloride channels (CaCC and ORCC), respectively [1-3].

References

1. Shimizu, T., Sakai, H., et al. Am. J. Physiol. Cell Physiol., 2013, 304, C748.

2. Sato-Numata, K., Numata, T., et al. Pflugers Arch., 2013 (in press);

3. Okada, T., Akita, T., et al. J. Physiol Sci, 2013, 63 (Suppl 1), S133 (Abstract).

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Бюллетень сибирской медицины, 2013, том 12, № 4, с. 24-68