Receptor-Operated Regulation of ATP-Sensitive K+ Channels Via Membrane Phospholipid Metabolism
ATP-sensitive K+ channels (KATP channels) regulate insulin secretion by coupling intracellular metabolic changes to excitability of the plasma membrane in pancreatic β-cells. The channels are closed when extracellular glucose levels are elevated due to enhanced feature. By contrast, cardiac-type KATP channels, which open in response to metabolic stress during cardiac ischemia, shorten action potential durations. This may contribute to the cardioprotection by decreasing Ca2+ influx through sarcolemma. By sensing intracellular ATP levels or ATP / ADP ratios, changes in activity of KATP channels convert metabolic information into membrane excitability. In addition to channel regulation by nucleotide concentrations, the channel activity is also dependent on the concentrations of membrane phospholipids, including phosphatidyl inositol-4,5-bisphosphate (PIP2). The levels of PIP2 in the membrane may determine the basal activity of the channels. This suggests that channel activity would be modulated by the pathway of receptor-coupled GTPbinding protein (G-protein) and phosphatidyl inositol phospholipase C (PI-PLC) stimulation, which brings about depletion of the membrane PIP2 pool. Thus, KATP channels not only provide interface of metabolic changes with electrical excitation, but also rapidly transmit extracellular signals through receptor-coupled Gprotein and PI-PLC pathway via PIP2 metabolism.
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Document Type: Review Article
Publication date: 01 February 2003
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