Modeling K(ATP) channel gating and its regulation.

ATP-sensitive potassium (K(ATP)) channels couple cell metabolism to plasmalemmal potassium fluxes in a variety of cell types. The activity of these channels is primarily determined by intracellular adenosine nucleotides, which have both inhibitory and stimulatory effects. The role of K(ATP) channels...

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Main Authors: Proks, P, Ashcroft, F
Format: Journal article
Language:English
Published: 2009
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author Proks, P
Ashcroft, F
author_facet Proks, P
Ashcroft, F
author_sort Proks, P
collection OXFORD
description ATP-sensitive potassium (K(ATP)) channels couple cell metabolism to plasmalemmal potassium fluxes in a variety of cell types. The activity of these channels is primarily determined by intracellular adenosine nucleotides, which have both inhibitory and stimulatory effects. The role of K(ATP) channels has been studied most extensively in pancreatic beta-cells, where they link glucose metabolism to insulin secretion. Many mutations in K(ATP) channel subunits (Kir6.2, SUR1) have been identified that cause either neonatal diabetes or congenital hyperinsulinism. Thus, a mechanistic understanding of K(ATP) channel behavior is necessary for modeling beta-cell electrical activity and insulin release in both health and disease. Here, we review recent advances in the K(ATP) channel structure and function. We focus on the molecular mechanisms of K(ATP) channel gating by adenosine nucleotides, phospholipids and sulphonylureas and consider the advantages and limitations of various mathematical models of macroscopic and single-channel K(ATP) currents. Finally, we outline future directions for the development of more realistic models of K(ATP) channel gating.
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spelling oxford-uuid:73d7c226-fe17-45bf-93d8-f3b95800e5ea2022-03-26T19:59:01ZModeling K(ATP) channel gating and its regulation.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:73d7c226-fe17-45bf-93d8-f3b95800e5eaEnglishSymplectic Elements at Oxford2009Proks, PAshcroft, FATP-sensitive potassium (K(ATP)) channels couple cell metabolism to plasmalemmal potassium fluxes in a variety of cell types. The activity of these channels is primarily determined by intracellular adenosine nucleotides, which have both inhibitory and stimulatory effects. The role of K(ATP) channels has been studied most extensively in pancreatic beta-cells, where they link glucose metabolism to insulin secretion. Many mutations in K(ATP) channel subunits (Kir6.2, SUR1) have been identified that cause either neonatal diabetes or congenital hyperinsulinism. Thus, a mechanistic understanding of K(ATP) channel behavior is necessary for modeling beta-cell electrical activity and insulin release in both health and disease. Here, we review recent advances in the K(ATP) channel structure and function. We focus on the molecular mechanisms of K(ATP) channel gating by adenosine nucleotides, phospholipids and sulphonylureas and consider the advantages and limitations of various mathematical models of macroscopic and single-channel K(ATP) currents. Finally, we outline future directions for the development of more realistic models of K(ATP) channel gating.
spellingShingle Proks, P
Ashcroft, F
Modeling K(ATP) channel gating and its regulation.
title Modeling K(ATP) channel gating and its regulation.
title_full Modeling K(ATP) channel gating and its regulation.
title_fullStr Modeling K(ATP) channel gating and its regulation.
title_full_unstemmed Modeling K(ATP) channel gating and its regulation.
title_short Modeling K(ATP) channel gating and its regulation.
title_sort modeling k atp channel gating and its regulation
work_keys_str_mv AT proksp modelingkatpchannelgatinganditsregulation
AT ashcroftf modelingkatpchannelgatinganditsregulation