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Figure 8. Simulation for the effect of Zn2+ on the quasi– steady state activation curve of the slow gate. Activation curves were generated based on Scheme SI (A) and Scheme III (B) in the presence of 0, 10, and 100 μM Zn2+ at 20° (left), 24° (middle), and 28°C (right). The ratio of the occupation probability of any two states, A and B, is assumed to be of the form: 1/KAB = PA/PB = exp(−ΔGAB/RT) = exp(ΔSAB/R − ΔHAB/RT + zABVF/RT), where KAB is the equilibrium constant, and ΔGAB, ΔSAB, and ΔHAB are the difference in Gibbs free energy, entropy, and enthalpy between the two states, respectively. R, T, and F have their usual meanings. V is the membrane voltage and zAB is the “gating valence” describing the voltage dependence of the transition A ↔ B. The values of the above parameters in the absence of Zn2+ were the same as those in a previous paper (Pusch et al., 1997) except for ΔHO1O2. They are shown as follows (ΔH in kJ/mol, ΔS in kJ/mol/°K): (A) ΔHOI = −80, ΔSOI = −0.29, zOI = −2; (B) ΔHO1I1 = −77, ΔSO1I1 = −0.26, zO1I1 = 0, ΔHO1O2 = 10, ΔSO1O2 = 0, zO1O2 = −2, ΔHO2I2 = −78, ΔSO2I2 = −0.27, zO2I2 = 0. Assigning 10 kJ/mol for ΔHO1O2 makes all curves in B shift to the left by ∼40 mV so that the curves from modeling are more similar to the experimental data with respect to their positions along the voltage axis. It does not affect the effect of Zn2+, which shifts the curve from top to bottom. Even with this adjustment, the assigned values in B do not provide a superb prediction for the plateau at positive voltages as they give a much larger noninactivated fractional current than the data shown in Fig. 7. This difference is not important since the pattern of Zn2+ inhibition is basically the same as that in the experimental data. The numbers 0, 10, and 100 indicate Zn2+ concentrations.

Image published in: Chen TY (1998)

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