Responding to Changes in Metabolism

Science's STKE  09 Jul 2002:
Vol. 2002, Issue 140, pp. tw245-TW245
DOI: 10.1126/stke.2002.140.tw245

Cardiac adenosine triphosphate (ATP)-sensitive potassium channels (KATP) respond to decreases in cellular ATP by opening, which reduces cellular excitability. Thus, KATP channels serve as metabolic sensors. Abraham et al. calculated that the diffusion constants for the movement of ATP and adenosine diphosphate (ADP) between the cytosol and the plasma membrane of cardiomyocytes, where the KATP channel resides, are insufficient for simple diffusion to allow the channel to respond to changes in cytosolic ATP concentrations. They show that phosphate flux through creatine kinase (CK) altered sensitivity of the KATP channel for ATP, with ATP sensitivity highest under conditions of high flux through creatine kinase. Under hypoxic conditions, phosphoryl transfer through CK is inhibited, which leads to increased channel activity at lower concentrations of ATP than observed under normoxic conditions. In cells from mice deficient for the major cytosolic CK isoform in heart (M-CK), KATP channel activity was not inhibited by application of creatine phosphate, and the animals had electrically unstable hearts in response to metabolic stress.

M. R. Abraham, V. A. Selivanov, D. M. Hodgson, D. Pucar, L. V. Zingman, B. Wieringa, P. P. Dzeja, A. E. Alekseev, A. Terzic, Coupling of cell energetics with membrane metabolic sensing. J. Biol. Chem. 277, 24427-24434 (2002). [Abstract] [Full Text]