Figure 10. Summary and analysis of the suppression of the Ca²⁺ channel by low Na⁺ and pH.

A) Dose-response of [Na⁺]_o vs.: I_Ca measured with Cs⁺ substitution in ventricular cells (black trace and symbols, cf. Fig. 3A), I_Ba measured with sucrose substitution in the HEK cell expression system (red, cf. Fig. 6E), and I_Ba measured with Cs⁺ substitution in ventricular (green, cf.Fig. 7E). Solid curves are proportional to each other while the green dashed and dotted curves are cubic and linear in [Na⁺]_o, respectively. B) Model suggesting different degrees of penetration of cations into (Na⁺, H⁺) and through (Ca²⁺, Ba²⁺) the Ca²⁺ channel where carboxylates (Y) may provide a negatively charged environment with binding sites both within the selectivity filter (EEEE locus) and in the outer vestibule. C) Combined effects of [Na⁺]_o and pH on I_Ba based on Fig. 9G, but scaled to show the average response to low Na⁺ at pH 7.4. The data at different pH values were approximated with curves based on the logistic equation (A + B/(1+([H⁺]/K_D)ⁿ)) showing no significant change to the effective binding constant in at 145 (black, circle, K_D = 69±12 nM) vs. 10 mM [Na⁺]_o (red, circle, K_D = 90±8 nM). D) Conductance of the Ca²⁺ channel at different [Na⁺]_o and pH measured from the linear segment of I-V relations (~10–50 mV, cf. Fig. 9HI). E) pH- and Na⁺-induced shifts in V_0.5 of activation relative to V_0.5 at pH 7.4 and 145 mM [Na⁺]_o (Cf. Fig. 9H,I).