Figure 1.

Cartoon summarizing the effects of dystrophin deficiency on voltage-dependent sarcolemmal ion channel expression and function in a ventricular cardiomyocyte. In healthy cardiomyocytes, protein members of the dystrophin-associated protein complex (DAPC), such as dystrophin and syntrophin, interact with ion channels to ensure their proper cellular expression and function. Among those interactions, syntrophin binding to Na_v1.5 and K_ir2.1 is well-established (see manuscript text). For potential other interactions (indicated by arrows), the evidence is less strong. In case of dystrophin deficiency, the DAPC interactions with ion channels are disturbed, which results in alterations in the channel properties. A red circle around a particular ion channel represents the down-regulation of the expression of the respective protein, while a grey circle indicates that dystrophin deficiency does not (or is not known to) alter a channel’s or a channel subunit’s expression. Red and green arrows represent channel loss-of-function and gain-of-function, respectively. The light red arrow indicates potential channel loss-of-function, whereby the literature evidence is controversial. A grey arrow indicates unaltered channel function, or that the potential effects of dystrophin deficiency are unknown. The physiologically prevailing direction of current flow during an action potential through a particular ion channel (inward and/or outward) can be derived from the respective arrow head position(s). I_CaL—L-type Ca²⁺ current; I_CaT—T-type Ca²⁺ current; I_Na—Na²⁺ current; I_K1—inward rectifier K⁺ current; I_to—transient outward K⁺ current; I_K,slow—ultra-rapid delayed rectifying and slowly inactivating K⁺ current. The channel or channel subunit names in the circles are given according to IUPHAR nomenclature.