Figure 13. Evidence for and against Na/K pump - Na/Ca exchange cross-talk via submembrane Na changes.
(A) Standard cytoplasmic solution was modified to effectively buffer cytoplasmic free Ca to ~0.2 µM (25 mM EGTA + 6 mM Ca). Reverse Na/Ca exchange currents were activated repeatedly for 2 s before and after Na/K pump currents were activated for 15 s. Exchange currents, like C6-TPP currents in Figure 12, are suppressed immediately after pump activity and recover over 20 s. (B) K-free cytoplasmic solution was buffered to contain 0.5 µM free Ca, thereby supporting a large, continuous inward exchange current (i.e. Na influx and Ca extrusion). 50 mM EGTAi+ 35 mM Cai, 10 mM Nai, and 125 mM Nao. Inward exchange current was initially blocked, as indicated, by applying 4 mM Ni on the extracellular side. Pump current was then activated by extracellular K and exchanger block was released by removing Ni at the same time. Subsequently, Na/K pump current was activated once without and once with Na/Ca exchange block. The presence or absence of inward exchange current, before activation of pump current, does not affect the magnitude of peak pump currents. Composite results for 9 experiments are tabulated below the cartoon. (C) Predictions of a simple Na+ depletion model. Pump currents were simulated with a hyperbolic dependence on cytoplasmic Na+ (K50, 5 mM), and the cytoplasmic space was limited to a value of 3 pL to promote submembrane Na changes. When Na depletion during pump activity limits pump currents and suppresses reverse exchange currents, as in Panel A, forward exchange currents should very significantly enhance pump currents under the conditions of Panel B, and that is not the case.