Panel A: A schematic diagram of a couplon showing the interaction between transverse tubular CaV1.1 tetrads and ryanodine receptor channels. The diagram includes a regular pattern of interaction between these components. The transverse tubular (TT) region contains CaV1.1 tetrads represented by red circles. The couplon region in the middle shows a pattern of interaction between CaV1.1 tetrads and ryanodine receptor channels (RyR1), with CaV1.1 tetrads in red and RyR1 channels in green. The sarcoplasmic reticulum (SR) region is depicted on the right. Panel B: A line trace showing the time course of the net calcium release flux from the SR. The blue trace represents the flux, while the red trace shows the applied voltage step. The graph includes labels for the flux and voltage traces. Middle part: Illustrations of two types of RyR1 channels, labeled as V-type and C-type. Right part: Channel state diagrams for C-type and V-type RyR1 channels, showing states such as closed (C), open (O), and inactivated (I1 and I2). The diagrams describe the gating of each RyR1 channel in the cluster, which also exhibit allosteric interactions with neighboring channels.
Modelling the couplon as a large interactive channel cluster. (A) Schematic diagram derived from Block et al. (1988) and Rios and Pizarro (2026) of the couplon with its regular pattern of interaction (middle part) between TT CaV1.1 tetrads (red) and every other tetrameric RyR1 channel (green). (B) Left: Typical biphasic time course of the net Ca2+ release flux from the SR (blue trace) of a mouse interosseous muscle fiber obtained under voltage clamp conditions (own data). The red trace shows the applied voltage step (100 ms long, from −80 to +20 mV) recorded with one of the two intracellular micropipettes. Middle: The two types of RyR1 channels, i.e., with and without contact to CaV1.1 tetrads (termed V and C, respectively). Right: Channel state diagrams assigned to C- and V-type RyR1 in the model by Rios and Pizarro (2026) (C: closed, O: open, I: inactivated). These diagrams describe the gating of each RyR1 channel in the cluster. In addition, the model includes terms for allosteric interactions with each channel’s neighbor. In the model, the transient component of the Ca2+ release flux originates from the C-type channels (which are allowed to inactivate: states I1 and I2) and the tonic component from the V-type channels (which are assumed to exhibit no inactivation). The slow decline visible during the tonic component likely reflects SR depletion.