SUMO1 suppresses I_DR in hippocampal neurons. Neurons were studied under voltage clamp in whole cell mode, and native I_Na, I_KA, and I_DR were assessed for response to intracellular application of 75 pM SUMO1₁₀₁ (•), with heat-denatured SUMO1₁₀₁ (■, Rest), or 250 pM SENP1 (▴). I_DR was also assessed for response to 75 pM SUMO2₉₂ (△) or SUMO3₉₂ (▽). An ensemble current trace and mean I-V relationships and normalized G-V relationships are shown. Recording conditions and biophysical parameters for I_DR are shown in Table I; values for I_Na and I_KA are in Table S1. Bars represent 1 nA and 10 ms in A and 1 nA and 100 ms in B and C. (A) I_Na magnitude and I-V relationships were unaltered by SUMO1₁₀₁ or SENP1. Protocol: 50-ms test pulses to −10 from −80 mV every 10 s (n = 10 –14 cells). (B) I_KA magnitude and I-V relationships were unaltered by SUMO1₁₀₁ or SENP1. Protocol: 500-ms test pulses to +50 from −80 mV every 10 s to activate both I_KA and I_DR, followed by repetition with an additional 250-ms pulse to −30 mV before the test pulse to inactivate I_KA and isolate I_DR. I_KA was determined by subtracting I_DR from the total potassium current in the presence of 50 nM tetrodotoxin to remove contaminating sodium currents (n = 10–20 cells). (C) I_DR magnitude was augmented by SENP1, unaltered by heat-denatured SUMO1₁₀₁, and diminished by SUMO1₁₀₁. The difference in the midpoint of the G-V relationships with SENP1 (n = 20 cells) and SUMO₁₀₁ (n = 10 cells) was 36 ± 5 mV. (D) I_DR magnitude was diminished by SUMO2 and SUMO3. The difference in the midpoint of the G-V relationships between SENP1 (C) and SUMO2₉₂ (n = 10 cells) was 37 ± 7 mV, and it was 37 ± 1 mV between SENP1 and SUMO3₉₂ (n = 10 cells).