Cytoskeleton Regulation of Ion Channels

Cardiac arrhythmia is one of the leading causes of sudden death in developed countries, and results from abnormal cardiac electrical activity. Regular beat-to-beat cardiac excitability requires the coordinated activity of membrane bound ionophoric proteins which are channels and transporters. Aberrant currents can result from either changes in the gating properties of ionophores or altered trafficking to their appropriate membrane subdomain. Mutations in the genes of ionophoric proteins result in inherited human arrhythmogenic syndromes. While mutations of channel proteins can affect biophysical gating properties1, most inherited arrhythmia disorders likely result from altered protein trafficking rather than gating2-5. In addition, mutations in the proteins that make up the trafficking apparatus, namely the cytoskeletal and associated proteins, can also result in arrhythmia disorders.