Figure 3.

Voriconazole blocks TRPM1 currents in rod bipolar cells and TRPM3 currents in transfected CHO cells. (A) The TRPM1 currents in rod bipolar cells activated by puff application of 100 μM capsaicin were inhibited by co-application of voriconazole (90% inhibition ± 4% SEM, n = 7). Washout of voriconazole restored the capsaicin-activated current. (B) The TRPM3 currents were elicited by application of 35 μM PS in CHO cells transiently transfected with a plasmid encoding a TRPM3-mCherry fusion protein. Co-application of 100 μM voriconazole with PS dramatically reduced the TRPM3 current at both negative and positive voltages. Return to PS alone restored the TRPM3 current. Similar to the effect on TRPM1 in rod bipolar cells, voriconazole resulted in a near complete block of the TRPM3 current. Vertical spikes represent currents elicited in response to voltage ramps. (C) HEK293 cells transiently transfected to express EGFP-TRPM3 were stepped sequentially through the following solutions: Ringer's solution, 50 μM PS, 50 μM PS plus 100 μM voriconazole, 50 μM PS, and Ringer's solution. Currents were recorded to a voltage ramp for each solution. (D) The I-V relationship for the PS-induced current was calculated by subtracting the current recorded in Ringer's solution from the one recorded in 50 μM PS, as shown in red. The current induced by PS but blocked by voriconazole was calculated by subtracting the current in 50 μM PS plus 100 μM voriconazole from the one in 50 μM PS, as shown in black. The two subtracted currents look almost identical.