Abstract
Evolution has acted to shape the action potential in different regions of the heart in order to produce a maximally stable and efficient pump. This has been achieved by creating regional differences in ion channel expression levels within the heart as well as differences between equivalent cardiac tissues in different species. These region- and species-dependent differences in channel expression are established by regulatory evolution, evolution of the regulatory mechanisms that control channel expression levels. Ion channel auxiliary subunits are obvious targets for regulatory evolution, in order to change channel expression levels and/or modify channel function. This review focuses on the transmural gradients of ion channel expression in the heart and the role that regulation of auxiliary subunit expression plays in generating and shaping these gradients.