Journal of Biological Chemistry
Volume 287, Issue 44, 26 October 2012, Pages 37145-37153
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Molecular Biophysics
Acid-sensitive TWIK and TASK Two-pore Domain Potassium Channels Change Ion Selectivity and Become Permeable to Sodium in Extracellular Acidification*

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Two-pore domain K+ channels (K2P) mediate background K+ conductance and play a key role in a variety of cellular functions. Among the 15 mammalian K2P isoforms, TWIK-1, TASK-1, and TASK-3 K+ channels are sensitive to extracellular acidification. Lowered or acidic extracellular pH (pHo) strongly inhibits outward currents through these K2P channels. However, the mechanism of how low pHo affects these acid-sensitive K2P channels is not well understood. Here we show that in Na+-based bath solutions with physiological K+ gradients, lowered pHo largely shifts the reversal potential of TWIK-1, TASK-1, and TASK-3 K+ channels, which are heterologously expressed in Chinese hamster ovary cells, into the depolarizing direction and significantly increases their Na+ to K+ relative permeability. Low pHo-induced inhibitions in these acid-sensitive K2P channels are more profound in Na+-based bath solutions than in channel-impermeable N-methyl-d-glucamine-based bath solutions, consistent with increases in the Na+ to K+ relative permeability and decreases in electrochemical driving forces of outward K+ currents of the channels. These findings indicate that TWIK-1, TASK-1, and TASK-3 K+ channels change ion selectivity in response to lowered pHo, provide insights on the understanding of how extracellular acidification modulates acid-sensitive K2P channels, and imply that these acid-sensitive K2P channels may regulate cellular function with dynamic changes in their ion selectivity.

Biophysics
Electrophysiology
Ion Channels
Membrane Biophysics
Physiology
Potassium Channels
Reconstitution of Membrane Transporters
Ion Selectivity
K2P Channel
Two-pore Domain Potassium Channels

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*

This work was supported, in whole or in part, by National Institutes of Health Grant 1R01GM102943-01A1 (to H. C.) through the NIGMS. This work was also supported by American Heart Association (11GRNT7270014) (to H. C.).