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

Biochem Biophys Rep. 2022 Apr 8:30:101260. doi: 10.1016/j.bbrep.2022.101260. eCollection 2022 Jul.

Authors

Robert Bränström^{1

2}, Erik Berglund², Robin Fröbom², Ingo B Leibiger¹, Barbara Leibiger¹, Craig A Aspinwall³, Olof Larsson¹, Per-Olof Berggren¹

Affiliations

¹ The Rolf Luft Research Center for Diabetes and Endocrinology, Sweden.
² Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
³ Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, USA.

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; K(ATP), ATP-sensitive potassium channel; Kir, Inward rectifier K+ channel; SUR, subunit sulfonylurea receptor; Single channel kinetics; β-cells.