Receptor-operated regulation of ATP-sensitive K+ channels via membrane phospholipid metabolism.
ATP-sensitive K(+) channels (K(ATP)channels) regulate insulin secretion by coupling intracellular metabolic changes to excitability of the plasma membrane in pancreatic beta-cells. The channels are closed when extracellular glucose levels are elevated due to enhanced feature. By contrast, cardiac-type K(ATP) channels, which open in response to metabolic stress during cardiac ischemia, shorten action potential durations. This may contribute to the cardioprotection by decreasing Ca(2+) influx through sarcolemma. By sensing intracellular ATP levels or ATP/ADP ratios, changes in activity of K(ATP) 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 (PIP(2)). The levels of PIP(2) 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 GTP-binding protein (G-protein) and phosphatidyl inositol phospholipase C (PI-PLC) stimulation, which brings about depletion of the membrane PIP(2) pool. Thus, K(ATP) channels not only provide interface of metabolic changes with electrical excitation, but also rapidly transmit extracellular signals through receptor-coupled G-protein and PI-PLC pathway via PIP(2) metabolism.
Kakei
M
M
Department of Geriatric Medicine, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan. kakei@med.akita-u.ac.jp
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002462:Cell Membrane / Q000737:chemistry; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D010743:Phospholipids / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction
D010743:Phospholipids; D015221:Potassium Channels; D000255:Adenosine Triphosphate; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020962:Heterotrimeric GTP-Binding Proteins