Electrical signaling in the heart involves the passage of ions through ionic channels. The Na+, K+, Ca2+, and Cl− ions are the major charge carriers, and their movement across the cell membrane creates a flow of current that generates excitation and signals in cardiac myocytes. Ion channels are macromolecular pores that span the lipid bilayer of the cell membrane (Fig. 35-11). Conformational transitions change (gate) a single ion channel from closed to open, which allows selected ions to flow passively down the electrochemical activity gradient at a very high rate (>106 ions per second). The high transfer rates and restriction to “downhill” fluxes not stoichiometrically coupled to the hydrolysis of energy-rich phosphates distinguish ionic channel mechanisms from those of other ion-transporting structures, such as the sarcolemmal Na+,K+-adenosine triphosphatase (ATPase) or the sarcoplasmic reticular Mg2+,Ca2+-ATPase (SERCA). Ion …