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The 2P-domain K+ channels: role in apoptosis and tumorigenesis

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Abstract

Two-pore (2P)-domain K+ channels have been shown recently to play a critical role in both cell apoptosis and tumorigenesis. The activity of two-pore, (TWIK)-related acid-sensitive-3 (TASK-3) K+ channels, is responsible for K+-dependent apoptosis of cultured cerebellar granule neurons. Neuron death can be prevented by conditions that specifically reduce K+ efflux through the TASK-3 channels. Moreover, genetic transfer of TASK subunits into hippocampal neurons that lack TASK-3, induces apoptosis. These results indicate a direct link between TASK K+ channel activity and the physiological process of programmed cell death. The TASK-3 K+ channel gene has also been shown to be amplified genomically and over-expressed in a significant number of breast tumours. TASK-3 has a potent oncogenic potential that appears to be related directly to its K+ channel function. In the present review, we will examine the pro-apoptotic and oncogenic properties of TASK-3. We will discuss: (1) the molecular and functional properties of the novel family of mammalian 2P domain K+ channels; (2) the role of TASK-3 in cerebellar granule neuron apoptosis and (3) the role of TASK-3 in breast tumorigenesis.

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Acknowledgements

We are grateful to Eric Honoré for his valuable comments and suggestions on this review. Funding for this work was provided by the CNRS and the Paul Hamel Institute.

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  1. Institut de Pharmacologie Moléculaire et Cellulaire, CNRS-UMR 6097, 660 route des Lucioles, Sophia Antipolis, 06560, Valbonne, France

    Amanda J. Patel & Michel Lazdunski

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  1. Amanda J. Patel
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Correspondence to Amanda J. Patel.

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Patel, A.J., Lazdunski, M. The 2P-domain K+ channels: role in apoptosis and tumorigenesis. Pflugers Arch - Eur J Physiol 448, 261–273 (2004). https://doi.org/10.1007/s00424-004-1255-8

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