Spassova M , Lu Z .

GM-55560 NIGMS NIH HHS , HL07027 NHLBI NIH HHS , R01 GM055560 NIGMS NIH HHS , T32 HL007027 NHLBI NIH HHS

	Figure 1. Voltage and extracellular K+ dependence of ROMK1 channel blockade by internal TEA. (A and D) Macroscopic I-V curves of ROMK1 channels recorded in the inside-out configuration in various [TEA]int. [K+]int was 100 mM and [K+]ext was as indicated. (B and E) Fractions of unblocked currents (I/Io) obtained from A and D were plotted against [TEA]int for several membrane voltages (Vm). Curves superimposed on the data correspond to least-squares fits using I/I0 = TEAK obs/(TEAK obs + [TEA]int) (TEAK obs is the observed TEA equilibrium dissociation constant). (C and F) ln TEAK obs obtained from B and E were plotted against Vm, respectively. The lines superimposed on the data correspond to least-squares fits using the Woodhull equation (Woodhull, 1973), lnTEAK obs = lnTEAK obs (0 mV) − TEA(zδ)obsFVm/RT.
	Figure 2. Summary of extracellular K+ dependence of ROMK1 channel blockade by internal TEA. (A) TEAK (0 mV) was plotted against [K+]ext. The line corresponds to the least-squares fit of a linear equation. (B) TEA(zδ)obs (mean ± SEM, n = 5) was plotted against [K+]ext. The curve corresponds to the least-squares fit by the equation TEA(zδ)obs = {TEA(zδ)inf − TEA(zδ)0 [K+]ext}/([K+]ext + KK app) + TEA(zδ)0, where KK app is the apparent (empirical) dissociation constant for the binding of external K+ to the pore, while TEA(zδ)0 and TEA(zδ)inf are TEA(zδ)obs when concentrations of external K+ ([K+]ext) are zero and infinity, respectively. The fit gives that TEA(zδ)0 = 0.39, TEA(zδ)inf = 0.92, and KK app = 9.6 mM. The data points corresponding to 0 mM external K+ were obtained in a nominal K+ free solution.
	Figure 3. Voltage and extracellular K+ dependence of ROMK1 channel blockade by TEA derivatives. (A–H) Macroscopic I-V curves recorded in various concentrations of quaternary ammoniums with either 100 mM external K+ (left) or 4 mM external K+ (right). TMA, TPrA, TBA, and TPeA stand for tetramethylammonium, tetrapropylammonium, tetrabutylammonium and tetrapentylammonium, respectively. [K+]int was 100 mM and [K+]ext was as indicated.
	Figure 4. Summary of extracellular K+ dependence of ROMK1 channel blockade by TEA and its derivatives. QAK obs (0 mV) and QA(zδ)obs (mean ± SEM, n = 5) values obtained as described in Fig. 1.
	Figure 5. Voltage and extracellular K+ dependence of ROMK1 channel blockade by internal Mg2+. (A and B) Macroscopic I-V curves of ROMK1 channels recorded in various [Mg2+]int. [K+]int was 100 mM and [K+]ext was as indicated in the figure. (C and D) Fractions of unblocked currents (I/Io) obtained from A and B were plotted against [Mg2+]int for several membrane voltages. Curves superimposed on the data correspond to least-squares fits using I/I0 = MgK obs/ (MgK obs + [Mg2+]int). (E and F) ln MgKobs obtained from C and D were plotted against membrane voltage (Vm). The lines superimposed on the data correspond to least-squares fits using the Woodhull equation, ln MgK obs = ln MgK obs (0 mV) − Mg(zδ)obsF  Vm/ RT. (G) MgK (0 mV)obs and Mg(zδ)obs (mean ± SEM, n = 5) for both [K+]ext.
	Figure 7. A model for TEA binding to a pore with three K+ sites. The model, modified from the model in Fig. 6 B, has two K+ sites in the narrow region of the pore and a third site in a wider internal region where either K+ or TEA can bind.

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