Zifarelli G , Pusch M .

GGP04018 Telethon, TI_GGP04018 Telethon

	Figure 1. ATP stimulation of currents mediated by ΔR-CFTR. (A) Current recordings from an inside-out patch upon perfusion with control internal solution (left), and with solutions containing ATP as indicated in the panels. Voltage pulses are from −80 to 80 mV in 20-mV increments. Capacity transients are not subtracted. (B) ATP dependence of currents measured at 80 mV normalized to currents measured in 1 mM ATP. Error bars indicate SD (the data point at 1 mM has no error bar because it was used for the normalization). The solid line is the best fit of Eq. 2 with Kd = 38 μM and n = 0.63.
	Figure 2. Effect of ATP on the gating of hClC-1. (A) macroscopic current recordings from an inside-out patch upon perfusion with control internal solution (left), during application of 10 mM ATP (middle), and after washout (right). (B) Voltage dependence of the overall open probability obtained from the macroscopic currents in A as described in Materials and methods. Symbols are: square, control; circle, 10 mM ATP; triangle, wash. Lines are fits of Eq. 1 with the following parameters: control, V1/2 = −89 mV, Pmin = 0.14; 10 mM ATP, V1/2 = −88 mV, Pmin = 0.13; wash V1/2 = −87 mV, Pmin = 0.14. (C) Effect of ATP on the slow gating mechanism of hClC-1. Data are from the same patch and were obtained from tail currents preceded by a 200-μs pulse to 160 mV. Symbols are as in B. Lines are fits of Eq. 1 with the following parameters: control, V1/2 = −82 mV, Pmin = 0.59; 10 mM ATP, V1/2 = −81 mV, Pmin = 0.58; wash V1/2 = −78 mV, Pmin = 0.63.
	Figure 3. Statistical evaluation of the gating parameters V1/2 and Pmin at pH 7.3 obtained in control solution (n = 10) and in solutions containing 1 (n = 3), 5 (n = 5), or 10 mM ATP (n = 5). Mean values of V1/2 (A) and Pmin (B) obtained from the analysis of the overall gating mechanism of hClC-1. Mean values of V1/2 (C) and Pmin (D) obtained from the analysis of isolated slow gating mechanism of hClC-1. The values are not significantly different (P > 0.06 using Student's unpaired t test).
	Figure 4. Effect of ATP on the gating of hClC-1 at pH 6.2. Top panel, macroscopic current recordings from an inside-out patch upon perfusion with control internal solution at pH 7.3 (A), pH 6.2 (B), solution at pH 6.2 with 1 mM ATP (C), and after washout (D). (E) Voltage dependence of the overall open probability obtained from the macroscopic currents in the top panel as described in Materials and methods. Symbols are: square, internal solution at pH 6.2; circle, solution at pH 6.2 with 1 mM ATP. Lines are fits of Eq. 1 with the following parameters: solution at pH 6.2, V1/2 = −94 mV, Pmin = 0.50; solution at pH 6.2 with 1 mM ATP, V1/2 = −95 mV, Pmin = 0.43. (F) Effect of ATP at pH 6.2 on the slow gating mechanism of hClC-1. Data are from the same patch and were obtained from tail currents preceded by a 200-μs pulse to 160 mV. Symbols are as in E. Lines are fits of Eq. 1 with the following parameters: solution at pH 6.2, V1/2 = −98 mV, Pmin = 0.74; solution at pH 6.2 with 1 mM ATP, V1/2 = −93 mV, Pmin = 0.74.
	Figure 5. Statistical evaluation of the gating parameters V1/2 and Pmin obtained with internal solution at pH 6.2 without ATP and with 1 mM ATP. Mean values of V1/2 in the absence and in the presence of 1 mM ATP (n = 36 and n = 21, respectively) (A) and Pmin (n = 28 and n = 9, respectively) (B) obtained from the analysis of the overall gating mechanism of hClC-1. Mean values of V1/2 in the absence and in the presence of 1 mM ATP (n = 8 and n = 5, respectively) (C) and Pmin (n = 19 and n = 13, respectively) (D) obtained from the analysis of isolated slow gating mechanism of hClC-1. The values in the absence and in the presence of 1 mM ATP are not significantly different (P > 0.06 using Student's unpaired t test).

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