Figure 1. Compartmental model of Ca²⁺ cycling, based on structural organization of a ventricular myocyte.

A, schematic diagram of the structural organization of a ventricular myocyte. Sarcolemmal Ca²⁺-ATPase (PMCa), L-type Ca²⁺ channels (LCC), 3Na⁺/Ca²⁺ exchanger (NCX) and Ca²⁺ binding proteins (buffers) are expressed throughout the sarcolemma. T-Tubules run radially and flank each sarcomere. Ca²⁺ release channels (RyRs) are expressed in the junctional portion of the SR membrane which faces the T-tubular portion of the sarcolemma and bounds the calsequestrin (CSQN) containing J-spaces. The junctional portion of the SR membrane and corresponding T-tubular portion of the sarcolemma form the T-spaces (grey spaces enclosed by dashed boundaries). During uniform activation of all RyR, identical Ca²⁺ distribution can be assumed in all J-spaces and in all T-spaces. Given the structural periodicity of the myocyte, a cell average Ca²⁺ concentration in J-space (Ca_j) and T-space (Ca_t) can be defined. SR Ca²⁺-ATPase (SERCA) is expressed in the network portion of the SR membrane which encloses the N-space. M-space is separated by the network portion of the SR membrane from the N-space and contains Ca²⁺ sensitive contractile (troponin) and regulatory (calmodulin) proteins. ∑I_K and ∑I_Na are sum of trans-sarcolemmal K⁺ and Na⁺ fluxes, respectively. B, compartmental model of Ca²⁺ cycling based on the structural organization in panel A, when synchronized activation of RyR generates a uniform Ca²⁺ flux (J_jt) from J-space to T-space. The transsarcolemmal Ca²⁺ fluxes, which include currents via LCC (I_Ca) and NCX (I_NCX), are partitioned between T-space and M-space. The effects of the contractile and regulatory proteins on Ca²⁺ dynamics is accounted for by buffering fluxes in the M-space (J_bf,m), T-space (J_bf,t), and J-space (J_csqn). Ca²⁺ flux between M-space and N-space (J_mn) is carried by SERCA. Transfer of Ca²⁺ between T-space and M-space (J_tm) is proportional to the difference between Ca_t and Ca_m. Similarly, J_nj is proportional to the difference between Ca_n and Ca_j. Additional symbols are defined in the text. Computer code is available on the website http://rudylab.wustl.edu/research/cell/lrd2.htm.