Do age-associated changes of voltage-gated sodium channel isoforms expressed in the mammalian heart predispose the elderly to atrial fibrillation?

Figure 3 Loss of function effects of SCN5a mutations on channel gating. Top Left: Curves illustrating the fraction of channels activated (white squares) and the fraction of channels inactivated (grey squares) vs membrane potential. Orange squares represent the effect of loss of function mutation on channel activation, the white curve is shifted to the right demonstrating a delay; Top right: Orange squares here represent the effect of loss of function mutation on channel inactivation. The grey curve is shifted to the left demonstrating early inactivation. Both of these effects mean a reduction in Na⁺ availability and a decreased peak sodium current (Bottom left); Bottom right: A normal action potential (blue) juxtaposed alongside an action potential due to a loss of function mutation (orange). Action potential upstroke is diminished and slowed. Adapted from Wilde et al[75], 2018, with permission.