Sensitivity of a renal K+ channel (ROMK2) to the inhibitory sulfonylurea compound glibenclamide is enhanced by coexpression with the ATP-binding cassette transporter cystic fibrosis transmembrane regulator

Carmel M. Mcnicholas; William B. Guggino; Erik M. Schwiebert; Steven C. Hebert; Gerhard Giebisch; Marie E. Egan

doi:10.1073/pnas.93.15.8083

Sensitivity of a renal K⁺ channel (ROMK2) to the inhibitory sulfonylurea compound glibenclamide is enhanced by coexpression with the ATP-binding cassette transporter cystic fibrosis transmembrane regulator

Carmel M. Mcnicholas, William B. Guggino, Erik M. Schwiebert, Steven C. Hebert, Gerhard Giebisch, Marie E. Egan

School of Medicine

Research output: Contribution to journal › Article › peer-review

182 Scopus citations

Abstract

We demonstrate here that coexpression of ROMK2, an inwardly rectifying ATP-sensitive renal K⁺ channel (I_KATP) with cystic fibrosis transmembrane regulator (CFTR) significantly enhances the sensitivity of ROMK2 to the sulfonylurea compound glibenclamide. When expressed alone, ROMK2 is relatively insensitive to glibenclamide. The interaction between ROMK2, CFTR, and glibenclamide is modulated by altering the phosphorylation state of either ROMK2, CFTR, or an associated protein, as exogenous MgATP and the catalytic subunit of protein kinase A significantly attenuate the inhibitory effect of glibenclamide on ROMK2. Thus CFTR, which has been demonstrated to interact with both Na⁺ and Cl^- channels in airway epithelium, modulates the function of renal ROMK2 K⁺ channels.

Original language	English (US)
Pages (from-to)	8083-8088
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	93
Issue number	15
DOIs	https://doi.org/10.1073/pnas.93.15.8083
State	Published - Jul 23 1996

Keywords

ATP-sensitive K channel
Phosphorylation
Subunit interaction

ASJC Scopus subject areas

General

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10.1073/pnas.93.15.8083

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Mcnicholas, C. M., Guggino, W. B., Schwiebert, E. M., Hebert, S. C., Giebisch, G., & Egan, M. E. (1996). Sensitivity of a renal K⁺ channel (ROMK2) to the inhibitory sulfonylurea compound glibenclamide is enhanced by coexpression with the ATP-binding cassette transporter cystic fibrosis transmembrane regulator. Proceedings of the National Academy of Sciences of the United States of America, 93(15), 8083-8088. https://doi.org/10.1073/pnas.93.15.8083

Sensitivity of a renal K⁺ channel (ROMK2) to the inhibitory sulfonylurea compound glibenclamide is enhanced by coexpression with the ATP-binding cassette transporter cystic fibrosis transmembrane regulator. / Mcnicholas, Carmel M.; Guggino, William B.; Schwiebert, Erik M. et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 93, No. 15, 23.07.1996, p. 8083-8088.

Research output: Contribution to journal › Article › peer-review

Mcnicholas, CM, Guggino, WB, Schwiebert, EM, Hebert, SC, Giebisch, G & Egan, ME 1996, 'Sensitivity of a renal K⁺ channel (ROMK2) to the inhibitory sulfonylurea compound glibenclamide is enhanced by coexpression with the ATP-binding cassette transporter cystic fibrosis transmembrane regulator', Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 15, pp. 8083-8088. https://doi.org/10.1073/pnas.93.15.8083

Mcnicholas CM, Guggino WB, Schwiebert EM, Hebert SC, Giebisch G, Egan ME. Sensitivity of a renal K⁺ channel (ROMK2) to the inhibitory sulfonylurea compound glibenclamide is enhanced by coexpression with the ATP-binding cassette transporter cystic fibrosis transmembrane regulator. Proceedings of the National Academy of Sciences of the United States of America. 1996 Jul 23;93(15):8083-8088. doi: 10.1073/pnas.93.15.8083

Mcnicholas, Carmel M. ; Guggino, William B. ; Schwiebert, Erik M. et al. / Sensitivity of a renal K⁺ channel (ROMK2) to the inhibitory sulfonylurea compound glibenclamide is enhanced by coexpression with the ATP-binding cassette transporter cystic fibrosis transmembrane regulator. In: Proceedings of the National Academy of Sciences of the United States of America. 1996 ; Vol. 93, No. 15. pp. 8083-8088.

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abstract = "We demonstrate here that coexpression of ROMK2, an inwardly rectifying ATP-sensitive renal K+ channel (IKATP) with cystic fibrosis transmembrane regulator (CFTR) significantly enhances the sensitivity of ROMK2 to the sulfonylurea compound glibenclamide. When expressed alone, ROMK2 is relatively insensitive to glibenclamide. The interaction between ROMK2, CFTR, and glibenclamide is modulated by altering the phosphorylation state of either ROMK2, CFTR, or an associated protein, as exogenous MgATP and the catalytic subunit of protein kinase A significantly attenuate the inhibitory effect of glibenclamide on ROMK2. Thus CFTR, which has been demonstrated to interact with both Na+ and Cl- channels in airway epithelium, modulates the function of renal ROMK2 K+ channels.",

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AU - Giebisch, Gerhard

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AB - We demonstrate here that coexpression of ROMK2, an inwardly rectifying ATP-sensitive renal K+ channel (IKATP) with cystic fibrosis transmembrane regulator (CFTR) significantly enhances the sensitivity of ROMK2 to the sulfonylurea compound glibenclamide. When expressed alone, ROMK2 is relatively insensitive to glibenclamide. The interaction between ROMK2, CFTR, and glibenclamide is modulated by altering the phosphorylation state of either ROMK2, CFTR, or an associated protein, as exogenous MgATP and the catalytic subunit of protein kinase A significantly attenuate the inhibitory effect of glibenclamide on ROMK2. Thus CFTR, which has been demonstrated to interact with both Na+ and Cl- channels in airway epithelium, modulates the function of renal ROMK2 K+ channels.

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