Publications by authors named "S L Shyng"
Pancreatic K channel trafficking defects underlie congenital hyperinsulinism (CHI) cases unresponsive to the K channel opener diazoxide, the mainstay medical therapy for CHI. Current clinically used K channel inhibitors have been shown to act as pharmacochaperones and restore surface expression of trafficking mutants; however, their therapeutic utility for K trafficking impaired CHI is hindered by high-affinity binding, which limits functional recovery of rescued channels. Recent structural studies of K channels employing cryo-electron microscopy (cryoEM) have revealed a promiscuous pocket where several known K pharmacochaperones bind.
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- ATP-sensitive potassium (K) channels act as metabolic sensors that regulate potassium flow based on the energy status of the cell, influenced by levels of ATP and ADP.
- These channels are made up of specific subunits (Kir and SUR) that form different types with unique roles in various tissues, impacting processes like insulin release and heart function.
- The chapter outlines a protocol for using rubidium efflux assays, combined with advanced measurement techniques, to discover new compounds that could modulate the activity of K channels for potential treatments of related diseases.
is a foodborne pathogen of concern in dairy processing facilities, with the potential to cause human illness and trigger regulatory actions if found in the product. Monitoring for spp. through environmental sampling is recommended to prevent establishment of these microorganisms in dairy processing environments, thereby reducing the risk of product contamination.
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- ATP-sensitive potassium (K) channels, made of Kir6.2 and SUR1 subunits, are crucial for insulin secretion in pancreatic beta cells, with their activity influenced by molecules like PIP and ATP.
- A new cryoEM structure reveals how a neonatal diabetes mutation (Kir6.2-Q52R) affects K channel function by showing binding sites for PIP that alter channel activity and stabilization.
- The study highlights the cooperation between Kir6.2 and SUR1 in regulating channel activity and explains how this process can lead to neonatal diabetes by destabilizing ATP binding.
K channels are ligand-gated potassium channels that couple cellular energetics with membrane potential to regulate cell activity. Each channel is an eight subunit complex comprising four central pore-forming Kir6 inward rectifier potassium channel subunits surrounded by four regulatory subunits known as the sulfonylurea receptor, SUR, which confer homeostatic metabolic control of K gating. SUR is an ATP binding cassette (ABC) protein family homolog that lacks membrane transport activity but is essential for K expression and function.
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