Table 2.

Effect of 10 µM NS5806 on K_v4.3 co-expressed with different subunits

Kv4.3+	−	DPP6	KCNE2	KCNE3	DPP6/KCNE3	KChIP2/DPP10
Peak current (µA) control	14.4 ± 2.0	20.4 ± 1.4	12.1 ± 1.9	1.8 ± 0.18	37.8 ± 6.8	14 ± 1.4
10 µM NS5806	6.6 ± 1.3 (8)**	11.0 ± 1.7 (9)***	7.5 ± 1.5 (6)**	1.3 ± 0.28 (8)*	23.6 ± 5.8 (8)**	10.4 ± 1.1 (5)**
Decay τ (ms) control	42.4 ± 2.1	37.7 ± 2.7	66.4 ± 13.8	55.1 ± 4.7	31.0 ± 1.0	17.6 ± 0.8
10 µM NS5806	45.6 ± 3.6 (8)	28.8 ± 0.73 (9)*	52.4 ± 7–3 (6)	48.1 ± 1.9 (4)	28.2 ± 7.7 (8)*	11.9 ± 0.5 (5)***
Area (µA·ms–1) control	783 ± 102	939 ± 120	959 ± 251	176 ± 45	1415 ± 311	409 ± 23
10 µM NS5806	367 ± 59 (8)***	501 ± 88 (9)***	408 ± 88 (6)**	169 ± 49 (4)	877 ± 20 (9)**	188 ± 194 (5)***
V1/2 (mV) control	−56.8 ± 1.3	−75.2 ± 0.14	−59.6 ± 0.9	−60.1 ± 0.57	−78.6 + 0.3	−72.8 ± 0.5
10 µM NS5806	−80.7 ± 2.7 (8)***	−82.2 ± 0.14 (8)***	−79.9 ± 1.1 (6)***	−78.4 ± 1.1 (8)***	−81.7 ± 0.2 (9)***	−80.6 ± 0.4 (5)***
Recovery τ (ms) control	480 ± 71	159 ± 3.8	235 ± 13.4	543 ± 24	176 ± 1.9	93.9 ± 2.1
10 µM NS5806	1459 ± 10 (8)***	239 ± 2.2 (5)***	492 ± 94.6 (6)***	1237 ± 123 (8)***	252 ± 2.4 (10)***	86.6 ± 6.3 (5)

Kv4.3+	KChIP2	KChIP2/DPP6	KChIP2/KCNE2	KChIP2/KCNE3	KChIP2/DPP6/KCNE3	KChIP2/DPP6/KCNE2
Peak current (µA) control	33.9 ± 2.9	33.1 ± 8.5	13.9 ± 1.47	1.8 ± 0.36 (5)	24.7 ± 3.9	33.9 ± 1.3
10 µM NS5806	35.9 ± 3.1 (7)**	33.0 ± 9.5 (9)	10.7 ± 1.09 (9)***	1.5 ± 0.36 (5)*	25.3 ± 4.0 (9)	25.9 ± 1.4 (5)**
Decay τ (ms) control	65.5 ± 6.3	33.6 ± 1.6	72.0 ± 6.5	187 ± 38	37.0 ± 2.1	44.3 ± 3.0
10 µM NS5806	90.0 ± 14.9 (7)***	45.3 ± 1.0 (10)***	78.0 ± 6.2 (9)*	199 ± 100(5)	42.1 ± 1.3 (9)*	44.9 ± 1.9 (5)
Area (µA·ms–1) control	2011 ± 219	1111 ± 304	1140 ± 98	195 ± 86	1190 ± 224	1804 ± 310
10 µM NS5806	2702 ± 316 (7)***	1752 ± 498 (10)*	822 ± 101 (9)*	153 ± 84 (5)	1622 ± 325 (9)**	1616 ± 98 (5)*
V1/2 (mV) control	−50.2 ± 0.7	−63 ± 0.4	−52.44 ± 1.3	−60.4 ± 1.3 (5)	−71.4 ± 0.6	−70.2 ± 0.4
10 µM NS5806	−58.9 ± 0.7 (7)***	−69 ± 0.3 (4)***	−71.9 ± 2.2 (9)***	−79.9 ± 1.5 (5)***	−77.8 ± 0.43 (9)***	−78.2 ± 0.2 (5)***
Recovery τ (ms) control	76.6 ± 2	42.6 ± 1.8	189.1 ± 5.5	522 ± 56 (5)	62.6 ± 1.6	68.6 ± 1.1
10 µM NS5806	274 ± 8.0 (7)***	66.8 ± 3.1 (8)***	547 ± 151 (9)***	1304 ± 134 (5)***	99.1 ± 1.6 (5)***	106 ± 4.5 (5)***

K_V4.3 channels expressed with different accessory subunits in Xenopus laevis oocytes. Currents were activated from a holding potential of −80 mV by a +40 mV step before and during application of 10 µM NS5806 and peak current amplitudes, time constants (τ) of current decay and total charge movement for the first 150 ms after complete activation was measured. Steady-state mid-inactivation (V_1/2) was evaluated from a holding potential of −100 mV by a series of 2 s prepulses from −100 to +40 mV followed by a +40 mV step. Boltzmann equations were fitted to normalized tail current amplitudes plotted as a function of the prepulse potential. Time constants (τ) for recovery from inactivation was determined by a two-pulse protocol; from a holding potential of −80 mV currents were activated by two test potentials to +40 mV with increasing interpulse time. The peak current at the second pulse was normalized to the first pulse and single exponential functions were fit to the data points. The different K_V4.3 β-subunit combinations were recorded on different days; however, the experiments in absence and presence of KChIP2 were in all cases performed in parallel and thus current amplitude and biophysical characteristics can be directly compared.

^*P < 0.05,

^**P < 0.01,

^***P < 0.001; significantly different in the absence and presence of NS5806.

DPP, dipeptidyl-peptidase.