RYR2s in cardiac ventricular myocytes. (A) Diagram of heart cell illustrating the locations of the TTs and SL with respect to the L-type Ca²⁺ channels (LCC), the junctional SR (jSR), the longitudinal SR, SERCA, RYR2 cluster, subspace, the Na⁺/Ca²⁺ exchanger (NCX), the plasmalemmal Ca²⁺ ATPase (PMCA), and a mitochondrion. (B) The dashed box (in A) is enlarged to reveal some of the changes that may occur in DMD. Micro-ruptures may lead to an increase in [Ca²⁺]_i and [Na⁺]_i, as may hyperactivity of stretch-activated channels (SAC); overexpression of caveoli, a putative site of NADPH oxidase, may also be involved. (C) Diagrammatic illustration how P_o^RYR2 sensitivity to [Ca²⁺]_i may be shifted to A (increase in sensitivity) or shifted to B (decrease in sensitivity). See Table I.