Figure 2.

Simulations of short-circuit interventions for HBE in physiological saline (left column) and in Cl⁻-free bath (right column). The vertical dashed lines correspond to the times when the pharmacological interventions occur. The identification and order of the pharmacological interventions are indicated by the bars in the bottom panels: amil (amiloride), forsk (forskolin), bum (bumetanide), EIPA, and actz (acetazolamide). Plots of I_sc, cell thickness (volume/surface area as projected on the plane of the epithelium), and intracellular pH are included. The reference simulation assumes basolateral Cl⁻ permeability of 5.2 × 10⁻⁸ m s⁻¹, whereas K⁺ permeates with a combination of fixed permeability of 8 × 10⁻⁸ m s⁻¹ and voltage-sensitive conductance constant $G_{\mathrm{K}}^{\mathrm{o}}$ = 10 S m⁻². Symbols indicate simulations in which different assumptions are made about the basolateral Cl⁻ permeability and K⁺ conductance, so that the effects of these particular quantities can be seen. The reference I_sc can be compared with error bars corresponding to data from Experiment 1 (16). Different symbols for the error bar correspond to different groups of data obtained sequentially (Table S3). For Experiment 2, fewer experimental data were reported (16) than for Experiment 1: in a group of 11 samples, forskolin increased I_sc by 6.3 ± 1.3 μA cm⁻², and in another group of five experiments, I_sc values after amiloride and forskolin introduction were 3.4 ± 0.3 and 7.4 ± 1 μA cm⁻², respectively. The other simulated results are features of the system not revealed by the experimental procedures. Thus, the top curves are validations of the model, whereas the other curves are new discoveries about the system behavior revealed in the simulations.