The regulation of ion channels and transporters by glycolytically derived ATP.
Glycolysis is an evolutionary conserved metabolic pathway that provides small amounts of energy in the form of ATP when compared to other pathways such as oxidative phosphorylation or fatty acid oxidation. The ATP levels inside metabolically active cells are not constant and the local ATP level will depend on the site of production as well as the respective rates of ATP production, diffusion and consumption. Membrane ion transporters (pumps, exchangers and channels) are located at sites distal to the major sources of ATP formation (the mitochondria). We review evidence that the glycolytic complex is associated with membranes; both at the plasmalemma and with membranes of the endo/sarcoplasmic reticular network. We examine the evidence for the concept that many of the ion transporters are regulated preferentially by the glycolytic process. These include the Na(+)/K(+)-ATPase, the H(+)-ATPase, various types of Ca(2+)-ATPases, the Na(+)/H(+) exchanger, the ATP-sensitive K(+) channel, cation channels, Na(+) channels, Ca(2+) channels and other channels involved in intracellular Ca(2+) homeostasis. Regulation of these pumps, exchangers and ion channels by the glycolytic process has important consequences in a variety of physiological and pathophysiological processes, and a better understanding of this mode of regulation may have important consequences for developing future strategies in combating disease and developing novel therapeutic approaches.
Dhar-Chowdhury
P
P
Pediatric Cardiology, NYU School of Medicine, 560 First Avenue TCH-521, New York, New York 10016, USA.
Malester
B
B
Rajacic
P
P
Coetzee
W A
WA
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002451:Cell Compartmentation; D002462:Cell Membrane / Q000378:metabolism; D006019:Glycolysis; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007473:Ion Channels / Q000378:metabolism*; D007474:Ion Exchange; D026901:Membrane Transport Proteins / Q000378:metabolism*; D015221:Potassium Channels; D017494:Proton Pumps / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D001786:Blood Glucose; D007328:Insulin; D007473:Ion Channels; D026901:Membrane Transport Proteins; D015221:Potassium Channels; D017494:Proton Pumps; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase