Phosphatidylinositol 4,5-Bisphosphate and Intracellular pH Regulate the ROMK1 Potassium Channel via Separate but Interrelated Mechanisms

Yuk-Man Leung; Wei-Zhong Zeng; Horng-Huei Liou; Christopher R Solaro; Chou-Long Huang

doi:10.1074/jbc.275.14.10182

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Phosphatidylinositol 4,5-Bisphosphate and Intracellular pH Regulate the ROMK1 Potassium Channel via Separate but Interrelated Mechanisms

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Phosphatidylinositol 4,5-Bisphosphate and Intracellular pH Regulate the ROMK1 Potassium Channel via Separate but Interrelated Mechanisms

Yuk-Man Leung, Wei-Zhong Zeng, Horng-Huei Liou, Christopher R Solaro and Chou-Long Huang

The Journal of biological chemistry, Vol.275(14), pp.10182-10189

04/07/2000

DOI: 10.1074/jbc.275.14.10182

PMID: 10744702

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Abstract

ROMK channels are responsible for K+ secretion in kidney. The activity of ROMK is regulated by intracellular pH (pHi) with acidification causing channel closure (effective pKa ∼6.9). Recently, we and others reported that a direct interaction of the channels with phosphatidyl-4,5-bisphosphate (PIP2) is critical for opening of the inwardly rectifying K+ channels. Here, we investigate the relationship between the mechanisms for regulation of ROMK by PIP2 and by pHi. We find that disruption of PIP2-ROMK1 interaction not only decreases single-channel open probability (Po) but gives rise to a ROMK1 subconductance state. This state has an increased sensitivity to intracellular protons (effective pKa shifted to pH ∼7.8), such that the subconductance channels are relatively quiescent at physiological pHi. Open probability for the subconductance channels can then be increased by intracellular alkalinization to supra-physiological pH. This increase in Po for the subconductance channels by alkalinization is not associated with an increase in PIP2-channel interaction. Thus, direct interaction with PIP2 is critical for ROMK1 to open at full conductance. Disruption of this interaction increases pHisensitivity for the channels via emergence of the subconductance state. The control of open probability of ROMK1 by pHi occurs via a mechanism distinct from the regulation by PIP2.

Details

Title: Subtitle: Phosphatidylinositol 4,5-Bisphosphate and Intracellular pH Regulate the ROMK1 Potassium Channel via Separate but Interrelated Mechanisms
Creators: Yuk-Man Leung
Wei-Zhong Zeng
Horng-Huei Liou
Christopher R Solaro
Chou-Long Huang
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.275(14), pp.10182-10189
DOI: 10.1074/jbc.275.14.10182
PMID: 10744702
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: Elsevier Inc
Language: English
Date published: 04/07/2000
Academic Unit: Nephrology; Internal Medicine
Record Identifier: 9984094772602771

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