Fig. 4. Aminophylline and theophylline enhance the luminal Ca²⁺ activation of RyR2.

The effects of aminophylline (A) and theophylline (B) on single-channel activities of RyR2 were recorded in a symmetrical recording solution as described in Fig. 3. The Ca²⁺ concentration on both the cytosolic and luminal sides of the incorporated channel was first adjusted to ~46 nM (Aa, Ba). The channel was activated by 300 μM luminal Ca²⁺ (Ab, Bb). Aminophylline (Ac) or theophylline (Bc) was then added to the cytosolic side the channel in the presence of 300 μM luminal Ca²⁺ followed by a decrease of luminal Ca²⁺ to ~46 nM (Ad, Bd). A similar luminal Ca²⁺ dependence of activation by aminophylline or theophylline was observed in 5–6 RyR2 channels. A continuous recording is shown for each condition. The average recording time is 134 s for panel A and 96 s for panel B.