Figure 6. Caffeine shifts the Ca²⁺ dependence by promoting a transition out of a closed state.

(A) Representative current traces are shown before and after addition of 10 mM caffeine. Caffeine increased channel open probability after a latency of several seconds. (B) Average (± SE) open probability histogram, binned in 500 ms increments, shows enhanced channel activity 12 seconds following the addition of 10 mM caffeine. (C) Bar charts constructed of mean (± SE) open (left) and closed (right) dwell times before and after addition of 10 mM caffeine. Only closed times were affected by caffeine. (D) Open (left) and closed (right) time histograms before and after the addition of 10 mM caffeine. Each distribution was well fitted with a single exponential. Time constants are inset into each graph. Open time constants were unaltered, while the closed time constant was reduced, in the presence of caffeine. Like Ca²⁺, caffeine destabilizes the closed state, and thereby facilitates transitions into the open state. Traces are representative examples of at least 4 other patches.