Directionality in drug action on sodium-calcium exchange.
In pathological conditions, the exchanger may generate deleterious calcium entry. A drug that inhibited calcium entry, while still allowing transport of calcium out of the cell would then seem attractive. In fact, this is impossible for thermodynamic reasons. Inhibitors may appear to be more effective when the exchanger is operating in net calcium entry mode than in calcium exit mode. This is, however, always attributable to differences in conditions because there is strong internal sodium dependence of drug action on the exchanger. When the exchanger is operating near equilibrium, drug action is found to be equally effective in both directions.
Noble
D
D
Department of Physiology, University of Oxford, Parks Road, Oxford, OX1 3PT, UK. Denis.noble@physiol.ox.ac.uk
Blaustein
M P
MP
D019831:Sodium-Calcium Exchanger / Q000737:chemistry / Q000187:drug effects*; D013816:Thermodynamics
D019831:Sodium-Calcium Exchanger