Our findings demonstrated that the N996I KCNH2 mutation caused a similar (∼30 40%) IKr reduction in both mutated hiPSC- and hESC-derived CMs.
The Y26A mutation caused a moderate loss of activity.
Differential scanning calorimetry experiments revealed that the mutation caused a modest increase in thermodynamic stability of the Fab, a feature predicted by the computational model.
Thus, the F327A mutation caused a loss of catalytic function by distorting the abovementioned elements.
This mutation caused a 60% reduction in crosslinking, comparable in magnitude to its effect on the permanganate sensitivity of T+2 (Figure 2B).
Thus, the Q453E mutation caused a loss of about 50- and 5-folds of enzymatic efficacy, kcat/KM, for cGMP and cAMP, respectively.
These data demonstrated that Cx30 null mutation caused a deficit in GJ-mediated metabolite transfer among cells in the sensory epithelium of the cochlea.
The absence of a C4BP effect in cells from patients with CD40 mutations is more difficult to reconcile with our data, although it is possible that the mutation caused a more generalised defect rendering cells unresponsive to TNFr mediated stimuli.
While the E108K and E111K mutants enabled the interaction with the complex, although diminished, the D124K mutation caused a drastic decrease in the interaction with ISCU and NFS1 (Fig 3A).
The sst2Δ mutation caused a saturation of active G-proteins so that the internal gradient was too shallow (G-proteins were almost fully active at both front and back) to be amplified by the downstream mechanisms.
Expression of the Glu379 insertion mutation caused a significant reduction in the total number of amperometric spikes per stimulus in comparison to controls in a direct comparison of responding cells (Figure 3B); however, it should be noted that this effect is likely underrepresented as the majority of Glu379 expressing cells produced no amperometric response.
