FIGURE 1.

T-tubule structure and key proteins involved in excitation-contraction (EC) coupling in the cardiomyocyte. A schematic overview of the t-tubule network is provided in the upper panel, while an enlargement of the indicated region is provided below to illustrate positioning of EC coupling proteins. EC coupling is initiated as Na⁺ channels are opened, and the cell membrane depolarizes during the action potential. This depolarization triggers the opening of voltage-gated L-type Ca²⁺-channels (LTCCs) in the t-tubules, and subsequent Ca²⁺-induced Ca²⁺ release from the SR through the opening of Ryanodine Receptors (RyRs). This process occurs at specialized junctions called dyads, where LTCCs and RyRs are in close proximity. After released Ca²⁺ binds to the myofilaments to trigger contraction, Ca²⁺ is recycled into the SR by the sarco-endoplasmic reticulum ATPase (SERCA), and removed from the cell by the Na⁺-Ca²⁺ exchanger (NCX) and the plasma-membrane Ca²⁺ ATPase. NCX activity is critically regulated by Na⁺ levels, set by the Na⁺ channel and the Na⁺-K⁺ ATPase within t-tubules. Created with BioRender.com.