Fig. 3.

Bioelectricity encompasses several interrelated phenomena, including $V_{mem}$; ion channel, pump and transporter dynamics; and instructive correlations between downstream signaling regimes including pH and metabolism. This bioelectrical example simulation of Na⁺,K⁺-ATPase pumps, H⁺,K⁺-ATPase pumps, K⁺ and Na⁺ leak channels, and a Na/HCO3⁻ transporter, with bicarbonate buffer and metabolic production equations, is detailed in (A), and was simulated in BETSE. The simulation explored a series of 10 min interventions, each separated by 20 min, including: blocking K⁺ leak channels (i), opening Na⁺ leak channels (ii), blocking Na⁺,K⁺-ATPase pumps (iii), activating H⁺,K⁺-ATPase pumps (iv), and increasing extracellular K⁺ levels (v). $V_{mem}$, intracellular pH, and energy charge of the cell are shown in B, C and D, respectively. Blocking K⁺ leak channels depolarizes $V_{mem}$, and leads to an increase in both cytosolic pH and the energy charge of the cell (i). Opening Na⁺ leak channels also depolarizes $V_{mem}$, but leads to significant drops in cell pH and energy charge (ii). Blocking the Na⁺,K⁺-ATPase pump leads to slight $V_{mem}$ depolarization and significant increases in cell pH and energy charge (iii). Activating an H⁺,K⁺-ATPase has minimal effect on $V_{mem}$, but significantly increases cell pH and decreases energy charge (iv). Increasing extracellular K⁺ depolarizes $V_{mem}$ (v). Note that the molecular perspective of bioelectricity provides an accurate estimation of $V_{mem}$ ($V_{mem}$ BETSE and $V_{mem}$ Goldman series of B), while managing interventions that alter ion reversal potentials (B).