Figure 4. A proposed gating model for the mechanism of the closure of Cx43 gap junction channels by direct Ca²⁺/CaM binding.

In this model, connexin has one open (Mo) state and open closed state (M₁). The induction of a conformational change in the cytoplasmic loop (CL) of Cx43 through Ca²⁺/CaM binding, steric hindrance of CaM binding near the cytoplasmic opening of the transmembrane pore, or a combination of both steric hindrance and conformational gating mechanisms causes the closure of the channel. Addition of the Cx43-CL-derived peptides or a CaMi (CaM inhibitor e.g., CDZ), prevents the Ca²⁺/CaM-Cx43 cytoplasmic loop interaction which changes the status of the channel from closed (M₁) to the open (M₀) state.