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

Figure 2 Gain 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. Green squares demonstrate the effect of a gain of function mutation resulting in incomplete inactivation of sodium channels at higher membrane potentials. This results in a higher fraction of channels inappropriately activated for a longer period, therefore developing an enhanced late current (Bottom left); Top right: Curves illustrating the delayed inactivation of sodium channels due to gain of function mutations resulting in an increased window current where channels may reactivate, again leading to increased late current; Bottom right: A normal action potential (blue) and an action potential with a prolonged plateau and repolarisation phases (green) as a consequence of faulty sodium channel gating mechanics brought about by gain of function mutations in SCN5a gene leading to aberrant sodium currents. Adapted from Wilde et al[75], 2018, with permission.