Fig. 5.

The slow mode of flecainide block is a closed-channel block as described by the scheme in (A). In the reaction scheme, the dashed rectangle encloses open and closed states of the RyR2 that appear as bursts of activity between slow-mode blocking events (defined here as closures >200 ms). According to this scheme, R_Son increases with RyR2 closed probability and with [flecainide]. (B) The on-rate R_Son increases with RyR2 closed probability within bursts, regardless of cytosolic (cyt) [Ca²⁺] and [Mg²⁺] or the presence of caffeine (caf). (C) The on-rate R_Son increases proportionally with [flecainide] (proportionality indicated by the dashed line). (D) Confirms that the rate constants for slow flecainide block [see equations in (A)] do not depend on cytosolic [Mg²⁺].