Fig. 4.

I_HERG is affected by physiological ceramide concentrations. A: dose-response relationships for the effect of Cer on slow and fast τ, V_1/2, and inhibition. The %effect values were normalized to effect measured at 20 μM Cer. The smooth lines are fits to the data using the Hill equation to yield EC₅₀ values of 2.6, 2.8, 10.2, and 9.4 μM, and Hill coefficient values were 2.4, 2.7, 1.1, and 0.9 for fast τ, slow τ, V_1/2, and inhibition, respectively. The applied Cer concentrations were 1, 3, 5, 10, and 20 μM (n = 3, 3, 8, 8, and 6, respectively). B: Cer inhibits HERG window current. The holding potential was set to the voltage (usually −20 mV) generating maximum window current, which was measured before, during, and upon recovery from 10 μM Cer (n = 5). To confirm that HERG channels produced the window current, inhibition by a known HERG blocker, terfenadine (0.1 μM), is also presented (n = 5).