Figure 7.

Hypothetical model of dynamic, functional interaction between TRPC3 and NCX1. TRPC3-mediated inotropy (upper left) requires close spatial proximity to NCX1. Cytoplasmic Ca²⁺ concentration is elevated by (i) suppressed intracellular Ca²⁺ clearance through NCX1 and (ii) by the TRPC3 Ca²⁺conductance itself. NCX forward-mode Ca²⁺ extrusion is limited to negative potentials, leading to enhanced Ca²⁺ loading of the SR. Excessive activation of TRPC3 results in transient Ca²⁺ overload followed by both channel inactivation and rapid spatial uncoupling from NCX1. While SR loading slowly declines, rapid drop in local cytoplasmic Na⁺ at the exchanger is expected to transiently favour arrhythmogenesis by facilitation of NCX forward mode (upper right).