Inward and outward currents of native and cloned K(ATP) channels (Kir6.2/SUR1) share single-channel kinetic properties

Robert Bränström; Erik Berglund; Robin Fröbom; Ingo B Leibiger; Barbara Leibiger; Craig A Aspinwall; Olof Larsson; Per-Olof Berggren

doi:10.1016/j.bbrep.2022.101260

Inward and outward currents of native and cloned K(ATP) channels (Kir6.2/SUR1) share single-channel kinetic properties

Robert Bränström, Erik Berglund, Robin Fröbom, Ingo B Leibiger, Barbara Leibiger, Craig A Aspinwall, Olof Larsson, Per-Olof Berggren

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Abstract

Background: The ATP-sensitive K+ (K(ATP)) channel is found in a variety of tissues extending from the heart and vascular smooth muscles to the endocrine pancreas and brain. Common to all K(ATP) channels is the pore-forming subunit Kir6.x, a member of the family of small inwardly rectifying K+ channels, and the regulatory subunit sulfonylurea receptor (SURx). In insulin secreting β-cells in the endocrine part of the pancreas, where the channel is best studied, the K(ATP) channel consists of Kir6.2 and SUR1. Under physiological conditions, the K(ATP) channel current flow is outward at membrane potentials more positive than the K+ equilibrium potential around -80 mV. However, K(ATP) channel kinetics have been extensively investigated for inward currents and the single-channel kinetic model is based on this type of recording, whereas only a limited amount of work has focused on outward current kinetics.

Methods: We have estimated the kinetic properties of both native and cloned K(ATP) channels under varying ionic gradients and membrane potentials using the patch-clamp technique.

Results: Analyses of outward currents in K(ATP) and cloned Kir6.2ΔC26 channels, alone or co-expressed with SUR1, show openings that are not grouped in bursts as seen for inward currents. Burst duration for inward current corresponds well to open time for outward current.

Conclusions: Outward K(ATP) channel currents are not grouped in bursts regardless of membrane potential, and channel open time for outward currents corresponds to burst duration for inward currents.

Original language	English
Article number	101260
Number of pages	7
Journal	Biochemistry and Biophysics Reports
Volume	30
Early online date	8 Apr 2022
DOIs	https://doi.org/10.1016/j.bbrep.2022.101260
Publication status	Published (in print/issue) - 31 Jul 2022

Bibliographical note

Funding Information:
This work was supported by grants from the Swedish Research Council, The Skandia Insurance Company Ltd, the Swedish Diabetes association, Strategic research program in Diabetes at Karolinska Institutet, the Berth von Kantzow's Foundation, the ERC-2018-AdG 834860 EYELETS, Diabetes Wellness Foundation, Stitching af Jochnick Foundation, The Family Knut and Alice Wallenberg Foundation, the Novo Nordisk Foundation, Funds at Karolinska Institutet, the Tore Nilsson Foundation, the Söderberg Foundation, the Thuring Foundation, the Jeansson Foundations, the Åke Wiberg Foundation, Magn. Bergwall Foundations, the Stockholm County Council, the Family Erling-Persson Foundation, and the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health (R01EB007047).

Funding Information:
This work was supported by grants from the Swedish Research Council , The Skandia Insurance Company Ltd, the Swedish Diabetes association, Strategic research program in Diabetes at Karolinska Institutet , the Berth von Kantzow's Foundation, the ERC-2018-AdG 834860 EYELETS, Diabetes Wellness Foundation, Stitching af Jochnick Foundation , The Family Knut and Alice Wallenberg Foundation , the Novo Nordisk Foundation , Funds at Karolinska Institutet , the Tore Nilsson Foundation , the Söderberg Foundation, the Thuring Foundation, the Jeansson Foundations , the Åke Wiberg Foundation, Magn. Bergwall Foundations, the Stockholm County Council, the Family Erling-Persson Foundation, and the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health ( R01EB007047 ).

Publisher Copyright:
© 2022 The Authors

Keywords

ATP-sensitive K+ (K(ATP)) channel
β-cells
Single channel kinetics
ATP-sensitive K (K(ATP)) channel

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10.1016/j.bbrep.2022.101260

1-s2.0-S2405580822000607-mainFinal published version, 3.79 MBLicence: CC BY

Cite this

@article{ba54970f6b644508a7a2993618f90594,

title = "Inward and outward currents of native and cloned K(ATP) channels (Kir6.2/SUR1) share single-channel kinetic properties",

abstract = "Background: The ATP-sensitive K+ (K(ATP)) channel is found in a variety of tissues extending from the heart and vascular smooth muscles to the endocrine pancreas and brain. Common to all K(ATP) channels is the pore-forming subunit Kir6.x, a member of the family of small inwardly rectifying K+ channels, and the regulatory subunit sulfonylurea receptor (SURx). In insulin secreting β-cells in the endocrine part of the pancreas, where the channel is best studied, the K(ATP) channel consists of Kir6.2 and SUR1. Under physiological conditions, the K(ATP) channel current flow is outward at membrane potentials more positive than the K+ equilibrium potential around -80 mV. However, K(ATP) channel kinetics have been extensively investigated for inward currents and the single-channel kinetic model is based on this type of recording, whereas only a limited amount of work has focused on outward current kinetics.Methods: We have estimated the kinetic properties of both native and cloned K(ATP) channels under varying ionic gradients and membrane potentials using the patch-clamp technique.Results: Analyses of outward currents in K(ATP) and cloned Kir6.2ΔC26 channels, alone or co-expressed with SUR1, show openings that are not grouped in bursts as seen for inward currents. Burst duration for inward current corresponds well to open time for outward current.Conclusions: Outward K(ATP) channel currents are not grouped in bursts regardless of membrane potential, and channel open time for outward currents corresponds to burst duration for inward currents.",

keywords = "ATP-sensitive K+ (K(ATP)) channel, β-cells, Single channel kinetics, ATP-sensitive K (K(ATP)) channel",

author = "Robert Br{\"a}nstr{\"o}m and Erik Berglund and Robin Fr{\"o}bom and Leibiger, {Ingo B} and Barbara Leibiger and Aspinwall, {Craig A} and Olof Larsson and Per-Olof Berggren",

note = "Funding Information: This work was supported by grants from the Swedish Research Council, The Skandia Insurance Company Ltd, the Swedish Diabetes association, Strategic research program in Diabetes at Karolinska Institutet, the Berth von Kantzow's Foundation, the ERC-2018-AdG 834860 EYELETS, Diabetes Wellness Foundation, Stitching af Jochnick Foundation, The Family Knut and Alice Wallenberg Foundation, the Novo Nordisk Foundation, Funds at Karolinska Institutet, the Tore Nilsson Foundation, the S{\"o}derberg Foundation, the Thuring Foundation, the Jeansson Foundations, the {\AA}ke Wiberg Foundation, Magn. Bergwall Foundations, the Stockholm County Council, the Family Erling-Persson Foundation, and the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health (R01EB007047). Funding Information: This work was supported by grants from the Swedish Research Council , The Skandia Insurance Company Ltd, the Swedish Diabetes association, Strategic research program in Diabetes at Karolinska Institutet , the Berth von Kantzow's Foundation, the ERC-2018-AdG 834860 EYELETS, Diabetes Wellness Foundation, Stitching af Jochnick Foundation , The Family Knut and Alice Wallenberg Foundation , the Novo Nordisk Foundation , Funds at Karolinska Institutet , the Tore Nilsson Foundation , the S{\"o}derberg Foundation, the Thuring Foundation, the Jeansson Foundations , the {\AA}ke Wiberg Foundation, Magn. Bergwall Foundations, the Stockholm County Council, the Family Erling-Persson Foundation, and the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health ( R01EB007047 ). Publisher Copyright: {\textcopyright} 2022 The Authors",

year = "2022",

month = jul,

day = "31",

doi = "10.1016/j.bbrep.2022.101260",

language = "English",

volume = "30",

journal = "Biochemistry and Biophysics Reports",

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TY - JOUR

T1 - Inward and outward currents of native and cloned K(ATP) channels (Kir6.2/SUR1) share single-channel kinetic properties

AU - Bränström, Robert

AU - Berglund, Erik

AU - Fröbom, Robin

AU - Leibiger, Ingo B

AU - Leibiger, Barbara

AU - Aspinwall, Craig A

AU - Larsson, Olof

AU - Berggren, Per-Olof

N1 - Funding Information: This work was supported by grants from the Swedish Research Council, The Skandia Insurance Company Ltd, the Swedish Diabetes association, Strategic research program in Diabetes at Karolinska Institutet, the Berth von Kantzow's Foundation, the ERC-2018-AdG 834860 EYELETS, Diabetes Wellness Foundation, Stitching af Jochnick Foundation, The Family Knut and Alice Wallenberg Foundation, the Novo Nordisk Foundation, Funds at Karolinska Institutet, the Tore Nilsson Foundation, the Söderberg Foundation, the Thuring Foundation, the Jeansson Foundations, the Åke Wiberg Foundation, Magn. Bergwall Foundations, the Stockholm County Council, the Family Erling-Persson Foundation, and the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health (R01EB007047). Funding Information: This work was supported by grants from the Swedish Research Council , The Skandia Insurance Company Ltd, the Swedish Diabetes association, Strategic research program in Diabetes at Karolinska Institutet , the Berth von Kantzow's Foundation, the ERC-2018-AdG 834860 EYELETS, Diabetes Wellness Foundation, Stitching af Jochnick Foundation , The Family Knut and Alice Wallenberg Foundation , the Novo Nordisk Foundation , Funds at Karolinska Institutet , the Tore Nilsson Foundation , the Söderberg Foundation, the Thuring Foundation, the Jeansson Foundations , the Åke Wiberg Foundation, Magn. Bergwall Foundations, the Stockholm County Council, the Family Erling-Persson Foundation, and the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health ( R01EB007047 ). Publisher Copyright: © 2022 The Authors

PY - 2022/7/31

Y1 - 2022/7/31

N2 - Background: The ATP-sensitive K+ (K(ATP)) channel is found in a variety of tissues extending from the heart and vascular smooth muscles to the endocrine pancreas and brain. Common to all K(ATP) channels is the pore-forming subunit Kir6.x, a member of the family of small inwardly rectifying K+ channels, and the regulatory subunit sulfonylurea receptor (SURx). In insulin secreting β-cells in the endocrine part of the pancreas, where the channel is best studied, the K(ATP) channel consists of Kir6.2 and SUR1. Under physiological conditions, the K(ATP) channel current flow is outward at membrane potentials more positive than the K+ equilibrium potential around -80 mV. However, K(ATP) channel kinetics have been extensively investigated for inward currents and the single-channel kinetic model is based on this type of recording, whereas only a limited amount of work has focused on outward current kinetics.Methods: We have estimated the kinetic properties of both native and cloned K(ATP) channels under varying ionic gradients and membrane potentials using the patch-clamp technique.Results: Analyses of outward currents in K(ATP) and cloned Kir6.2ΔC26 channels, alone or co-expressed with SUR1, show openings that are not grouped in bursts as seen for inward currents. Burst duration for inward current corresponds well to open time for outward current.Conclusions: Outward K(ATP) channel currents are not grouped in bursts regardless of membrane potential, and channel open time for outward currents corresponds to burst duration for inward currents.

AB - Background: The ATP-sensitive K+ (K(ATP)) channel is found in a variety of tissues extending from the heart and vascular smooth muscles to the endocrine pancreas and brain. Common to all K(ATP) channels is the pore-forming subunit Kir6.x, a member of the family of small inwardly rectifying K+ channels, and the regulatory subunit sulfonylurea receptor (SURx). In insulin secreting β-cells in the endocrine part of the pancreas, where the channel is best studied, the K(ATP) channel consists of Kir6.2 and SUR1. Under physiological conditions, the K(ATP) channel current flow is outward at membrane potentials more positive than the K+ equilibrium potential around -80 mV. However, K(ATP) channel kinetics have been extensively investigated for inward currents and the single-channel kinetic model is based on this type of recording, whereas only a limited amount of work has focused on outward current kinetics.Methods: We have estimated the kinetic properties of both native and cloned K(ATP) channels under varying ionic gradients and membrane potentials using the patch-clamp technique.Results: Analyses of outward currents in K(ATP) and cloned Kir6.2ΔC26 channels, alone or co-expressed with SUR1, show openings that are not grouped in bursts as seen for inward currents. Burst duration for inward current corresponds well to open time for outward current.Conclusions: Outward K(ATP) channel currents are not grouped in bursts regardless of membrane potential, and channel open time for outward currents corresponds to burst duration for inward currents.

KW - ATP-sensitive K+ (K(ATP)) channel

KW - β-cells

KW - Single channel kinetics

KW - ATP-sensitive K (K(ATP)) channel

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U2 - 10.1016/j.bbrep.2022.101260

DO - 10.1016/j.bbrep.2022.101260

M3 - Article

C2 - 35434386

SN - 2405-5808

VL - 30

JO - Biochemistry and Biophysics Reports

JF - Biochemistry and Biophysics Reports

M1 - 101260

ER -

Inward and outward currents of native and cloned K(ATP) channels (Kir6.2/SUR1) share single-channel kinetic properties

Abstract

Bibliographical note

Keywords

UN SDGs

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