KV11.1, NaV1.5, and CaV1.2 Transporter Proteins as Antitarget for Drug Cardiotoxicity

Figures

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  Figure 1. Drugs withdrawn from market due to proarrhythmic effect (purple), myocardial infarction (green), torsadogenic potential, i.e., QT interval prolongation and torsade the points (TdP) effect (red).

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  Figure 2. Schematic view of the structure’s subunits of cardiac ion channels. α1−subunits of K+ channels consist of one single subunit (domain or core motif), while Na+ channels and Ca2+ channels consist of four serially-linked homologous domains (I–IV). Each subunit contains six transmembrane segments (S1–S6). The S5 and S6 segments and the membrane-associated pore loop (often called the P loop or P segment or P region) between them form the central pore through which ions flow down their electrochemical gradient. The S4 transmembrane domain is the voltage-sensor (gating modifier). K+ channel is a tetramer assembly of α subunits. While Na+ and Ca2+ channels consist of four subunits co-assembled to form a single functional channel. The β, α2δ, and γ subunits enhance cell surface expression and modulate the voltage dependence and gating kinetics of the α1 subunits and channel sensitivity to endogenous ligands and pharmacological agents. These accessory subunits determine ion channel tissue specificity.

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  Figure 3. Classification of cardiac antiarrhythmic drugs.