Figure 4.
Figure 4. A region of the HCN4 C terminus distal to the CNBD mediates ligand-independent relief of autoinhibition in CHO cells. (A and B) Schematics and voltage dependence of HCN4-Δ719 and HCN4-Δ1012 channels. In the schematic illustrations, the thick bold lines represent the CNBD, the red “X’s” indicate the deleted portion of the distal C terminus, and the green line illustrates the region between 719 and 1012. The voltage dependence of activation was determined from tail currents after 3-s hyperpolarizing steps to the indicated voltages in whole cell recordings from CHO cells expressing HCN4-Δ719 (A) or HCN4-Δ1012 (B) in the absence (black) or presence (red) of 1 mM cAMP in the patch pipette. (C) Amino acid sequence alignment of the distal C terminals of HCN1-HCN4, beginning just after the CNBD. Residues shown are HCN1 588–750, HCN2 641–758, HCN3 551–680, and HCN4 719–1012. Gray shading indicates identical residues.

A region of the HCN4 C terminus distal to the CNBD mediates ligand-independent relief of autoinhibition in CHO cells. (A and B) Schematics and voltage dependence of HCN4-Δ719 and HCN4-Δ1012 channels. In the schematic illustrations, the thick bold lines represent the CNBD, the red “X’s” indicate the deleted portion of the distal C terminus, and the green line illustrates the region between 719 and 1012. The voltage dependence of activation was determined from tail currents after 3-s hyperpolarizing steps to the indicated voltages in whole cell recordings from CHO cells expressing HCN4-Δ719 (A) or HCN4-Δ1012 (B) in the absence (black) or presence (red) of 1 mM cAMP in the patch pipette. (C) Amino acid sequence alignment of the distal C terminals of HCN1-HCN4, beginning just after the CNBD. Residues shown are HCN1 588–750, HCN2 641–758, HCN3 551–680, and HCN4 719–1012. Gray shading indicates identical residues.

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