Figure 8.

Terikalant at 10 μM inhibits I_K1 without affecting I_K and I_Ca. (a) I_K1 was measured by applying a 500-ms ramp from 10 mV to −110 from a potential of −40 mV. Terikalant (10 μM) inhibited the outward current more than the inward current, although in both cases inhibition was significant (P<0.05, one-tailed paired t-test on the individual points). The current was maximally reduced by 89±4% at −30 mV. The effect of terikalant was reversible and following 10 min of washout of the drug, the current had almost returned to control levels (n=10 for control and 10 μM terikalant, and n=9 for washout). (b) The average, over 2 min, of 60 consecutive I_Kr current traces in control, and in the presence of 10 and 100 μM terikalant. At 10 μM, I_Kr was unaffected but at 100 μM the current was reduced by 51%. I_Kr was measured by stepping to −40 mV for 50 ms from a holding potential of −70 mV and then applying a 250-ms duration pulse to +20 mV. The zero I_Kr current level is shown by the dotted line, marked 0. The current at −40 mV, shown before and after the 250-ms pulse, is reduced by both 10 and 100 μM terikalant (lower most trace), due to inhibition of I_K1. (c) The average over 2 min of 24 consecutive I_Ca current traces in control, and in the presence of 10 and 100 μM terikalant. I_Ca was also unaffected by 10 μM terikalant, although 100 μM inhibits the current by 26%. The dotted line, marked 0, is the zero current level. I_Ca was measured by applying a 300-ms duration pulse to +10 mV from a holding potential of −70 mV.