Molecular Determinants of Interactions between the N-Terminal Domain and the Transmembrane Core That Modulate hERG K+ Channel Gating
Figure 2
The recombinant N1-135/YFP fragment does not restore slow deactivation of hERG channels carrying a Y542C mutation in the S4–S5 linker.
A. Schematic of the WT hERG K+ channel and representative tail currents obtained with the indicated protocol are shown for comparison. B. Lack of effect of the N1-135/YFP recombinant fragment on deactivation kinetics of Y542C channels. Channel schematics and families of representative tail currents are shown on the left. Black dots indicate the approximate position of the Y542C mutation. Plots of fast deactivation time constants at different repolarization voltages are shown on the right. Open and closed symbols correspond to data obtained in the absence or the presence of the recombinant fragment, respectively. Data from WT hERG channels are also shown as a dotted line for comparison. n = 10 and 6 for Y52C and Y542C+eag, respectively. C. The N1-135/YFP recombinant fragment does not slow down deactivation kinetics of Δ2-135 channels carrying a Y542C mutation in the S4–S5 linker. Open and closed symbols correspond to data obtained with the Δ2-135 plus Y542C construct in the absence and the presence of the recombinant fragment, respectively. Data from WT, Δ2-135 and Y542C hERG channels are also shown as dotted and dashed lines for comparison. n = 6 and 5 for Δ2-135/Y52C and Δ2-135/Y542C+eag, respectively. D. The presence of the N1-135/YFP recombinant fragment fully restores slow deactivation gating of Δ2-135 channels carrying the G546C mutation in the S4–S5 linker. Open and closed symbols correspond to data obtained with the Δ2-135 plus G546C construct in the absence or the presence of the recombinant fragment, respectively. Data from WT and Δ2-135 hERG channels are also shown as dotted and dashed lines for comparison. n = 6 and 8 for Δ2-135/G546C and Δ2-135/Y546C+eag, respectively.