Figure 4.

GxTx accelerates Kv2.1 deactivation kinetics in whole-cell recordings. (A) Current in response to a series of voltage steps from +40 mV down to −100 mV in −10-mV increments following a 50-ms prepulse to +80 mV. Current recorded in indicated concentration of GxTx. Voltage stimuli colored identically in all panels. (B) Values of τ_deact from fits of Eq. 4. Symbols denote individual cells. (C) Deactivation current response to voltage steps from −80 mV down to −100 or 0 mV. Gray, vehicle; pink, 10 nM GxTx; red, 100 nM; dark red, 1 µM. Dotted lines, zero current level. Lines, fit of Eq. 4 (−100 mV vehicle: A = −210.8 ± 0.4 pA, B = −12.3 ± 0.1 pA, τ_deact = 2.67 ± 0.01 ms; −100 mV 10 nM: A = −140.4 ± 0.7 pA, B = −15.6 ± 0.1 pA, τ_deact = 1.60 ± 0.01 ms; −100 mV 100 nM: A = −66 ± 1 pA, B = −6.4 ± 0.1 pA, τ_deact = 0.69 ± 0.02 ms; −100 mV 1 µM: A = −80 ± 1 pA, B = −5.1 ± 0.1 pA, τ_deact = 0.91 ± 0.02 ms; 0 mV vehicle: A = 176.1 ± 0.5 pA, B = 531.3 ± 0.6 pA, τ_deact = 7.75 ± 0.07 ms; 0 mV 10 nM: A = 267.6 ± 0.5 pA, B = 171.4 ± 0.5 pA, τ_deact = 6.96 ± 0.04 ms; 0 mV 100 nM: A = 217.6 ± 0.5 pA, B = 16.5 ± 0.2 pA, τ_deact = 3.72 ± 0.02 ms; 0 mV 1 µM: A = 229.1 ± 0.5 pA, B = 13.8 ± 0.2 pA, τ_deact = 3.55 ± 0.02 ms). (D) Geometric mean of τ_deact from cells in B. Black circles, control; pink triangles, 10 nM GxTx; red inverted triangles, 100 nM; dark red diamonds, 1 µM. Lines, fit of Eq. 8 (vehicle: τ_0mV = 31 ± 2 ms, z = −0.60 ± 0.02 e₀; 100 nM: τ_0mV = 6.2 ± 0.2 ms, z = −0.53 ± 0.02 e₀; 1 µM τ_0mV = 6.1 ± 0.1 ms, z = −0.50 ± 0.02 e₀). (E) Deactivation curves calculated from Eq. 4 when τ_deact is varied. Calculation for four independent deactivation gates closing with rate k_gate where τ_deact = (k_gate1 + k_gate2 + k_gate3 + k_gate4). Toxin binding accelerates k_gate fourfold.