Simulation of Na/Ca exchange activity during ischemia.
Simulation of sodium-calcium exchange activity during the rise of intracellular sodium that occurs during ischemia suggests that the exchanger may not reverse direction except transiently during calcium oscillations. This conclusion depends on the presence of a small resting leak of calcium into the cell, consistent with radioactive calcium flux measurements. The conditions for intracellular calcium to rise to around 3 microM were explored. A combination of extracellular potassium accumulation and extracellular sodium depletion is sufficient to explain this result. The computations also show a counterintuitive result concerning the role of the exchanger in the mechanism of calcium oscillations. Reducing its activity would be expected to enhance these oscillations, whereas increasing it can reduce or suppress oscillations. If such oscillations play a role in acute ischemic arrhythmias, then block of Na/Ca exchange may not be therapeutic.
Noble
Denis
D
University Laboratory of Physiology, Oxford University, Oxford OX1 3PT, UK. denis.noble@physiol.ox.ac.uk
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism*; D005110:Extracellular Space / Q000502:physiology; D007511:Ischemia / Q000503:physiopathology*; D007700:Kinetics; D008955:Models, Cardiovascular; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000502:physiology*
D019831:Sodium-Calcium Exchanger; D012964:Sodium; D002118:Calcium