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Role of K2P channels in stimulus-secretion coupling

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Abstract

Two-pore domain K+ (K2P) channels are involved in a variety of physiological processes by virtue of their high basal activity and sensitivity to various biological stimuli. One of these processes is secretion of hormones and transmitters in response to stimuli such as hypoxia, acidosis, and receptor agonists. The rise in intracellular [Ca2+] ([Ca2+]i) that is critical for the secretory event can be achieved by several mechanisms: (a) inhibition of resting (background) K+ channels, (b) activation of Na+/Ca2+-permeable channels, and (c) release of Ca2+ from intracellular stores. Here, we discuss the role of TASK and TREK in stimulus-secretion mechanisms in carotid body chemoreceptor cells and adrenal medullary/cortical cells. Studies show that stimuli such as hypoxia and acidosis cause cell depolarization and transmitter/hormone secretion by inhibition of TASK or TREK. Subsequent elevation of [Ca2+]i produced by opening of voltage-dependent Ca2+ channels then activates a Na+-permeable cation channel, presumably to help sustain the depolarization and [Ca2+]i. Agonists such as angiotensin II may elevate [Ca2+]i via multiple mechanisms involving both inhibition of TASK/TREK and Ca2+ release from internal stores to cause aldosterone secretion. Thus, inhibition of resting (background) K+ channels and subsequent activation of voltage-gated Ca2+ channels and Na+-permeable non-selective cation channels may be a common ionic mechanism that lead to hormone and transmitter secretion.

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Acknowledgments

This work was made possible by a grant from NIH (HL-111497).

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  1. Dawon Kang

    Present address: Department of Physiology and Institute of Health Sciences, Gyeongsang National University School of Medicine, 816-15 Jinju-daero, Jinju, 660-290, South Korea

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  1. Department of Physiology and Biophysics, Chicago Medical School, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL, 60064, USA

    Donghee Kim

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“This article is published as part of the Special Issue on [K2P channels].”

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Kim, D., Kang, D. Role of K2P channels in stimulus-secretion coupling. Pflugers Arch - Eur J Physiol 467, 1001–1011 (2015). https://doi.org/10.1007/s00424-014-1663-3

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