Figure 5. Na/K pump currents in a mouse... | Rockefeller University Press

Figure 5.

$Na/K pump currents in a mouse myocyte, recorded as described previously (Lu et al., 2016).(A) Whole-cell recording of pump current with 20 mM cytoplasmic Na and 7 mM extracellular Na. (B) Pump current is activated six times by application of 7 mM K for 12 s in exchange for 7 mM Na. After the second application of K, cytoplasmic Ca (4 mM) is applied for 5 s, and reverse exchange current is activated, resulting in spontaneous myocyte beating for ∼10 s (not illustrated). Thereafter, peak pump current is increased ∼70%, pump current at 12 s is increased more than threefold, and current decay is decreased substantially. The stimulatory effects reverse completely within 2 min. (C) Semi-log plot of Na/K pump current decay before (1) and after (2) Ca application. Decay shows fast and slow components with time constants of ∼1.2 and 15 s. The fast component becomes smaller and the slow component becomes larger after Ca application. The slow component reflects Na exchange between the cytoplasm and the pipette tip. (D) Simulation of the model from Fig. 4. “Factive” is the fraction of pumps in the active state. To simulate the effect of Ca, the inactivation rate constant is decreased with no other parameter changes. Peak currents increase because pump failures promote accumulation of inactive pumps in the absence of extracellular K. Larger pump currents after decreasing inactivation result in greater depletion of cytoplasmic Na (see predicted cytoplasmic Na concentration). Predicted Na/K pump current match well the measured Na/K pump current transients.$

Na/K pump currents in a mouse myocyte, recorded as described previously ( Lu et al., 2016 ). (A) Whole-cell recording of pump current with 20 mM cytoplasmic Na and 7 mM extracellular Na. (B) Pump current is activated six times by application of 7 mM K for 12 s in exchange for 7 mM Na. After the second application of K, cytoplasmic Ca (4 mM) is applied for 5 s, and reverse exchange current is activated, resulting in spontaneous myocyte beating for ∼10 s (not illustrated). Thereafter, peak pump current is increased ∼70%, pump current at 12 s is increased more than threefold, and current decay is decreased substantially. The stimulatory effects reverse completely within 2 min. (C) Semi-log plot of Na/K pump current decay before (1) and after (2) Ca application. Decay shows fast and slow components with time constants of ∼1.2 and 15 s. The fast component becomes smaller and the slow component becomes larger after Ca application. The slow component reflects Na exchange between the cytoplasm and the pipette tip. (D) Simulation of the model from Fig. 4. “F_active” is the fraction of pumps in the active state. To simulate the effect of Ca, the inactivation rate constant is decreased with no other parameter changes. Peak currents increase because pump failures promote accumulation of inactive pumps in the absence of extracellular K. Larger pump currents after decreasing inactivation result in greater depletion of cytoplasmic Na (see predicted cytoplasmic Na concentration). Predicted Na/K pump current match well the measured Na/K pump current transients.