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. 2015 Nov 3;8:63. doi: 10.3389/fnmol.2015.00063

FIGURE 5.

FIGURE 5

Molecular correlate for the WAG-HCN1 gain-of-function. (A) Cartoon depicting the N-termini of rat HCN1 (left) and WAG-HCN1 (right). The N-terminus of rat HCN1 has a length of 135 amino acids. WAG-HCN1 has a deletion of 37 amino acids and a novel polyserine motif of six amino acids. (B) Measurement of current amplitude of HCN1 and WAG-HCN1 48 h after injection and incubation in ND96 storage solution, supplemented with different protein kinase inhibitors (1 μM bisindolylmaleimide (BIS), 1 μM H-89, 10 μM genistein, or 1 μM staurosporine). Currents were normalized to the HCN1 construct incubated in normal storage solution. The number of experiments are indicated in the bar graphs. (C) Comparison of WAG-HCN1 (left) with a mutated WAG-HCN1 (HCN1-Δ37-aa) where the polyserine motif has been mutated to the wild-type sequence GNSVCF (right). This construct harbors only the deletion and not the polyserine stretch. (D) Current amplitudes of HCN1, WAG-HCN1 and HCN1-Δ37-aa analyzed at -130 mV. HCN1-Δ37-aa has a current amplitude similar to that of rat HCN1 (0.88 ± 0.08). The number of experiments are indicated in the bar graphs. ∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.001.