Activation of axonal Kv7 channels in human peripheral nerve by flupirtine but not placebo - therapeutic potential for peripheral neuropathies: results of a randomised controlled trial

Table 1 Electrical excitability parameters for myelinated axons in human sural nerve in vitro

	Baseline (n = 21)			Flupirtine 3μM (n = 7)			Flupirtine 10 μM (n = 8)			Flupirtine 30 μM (n = 16)			XE 911 10μM (n = 9)			ANOVA (df)F, p
Strength-duration time constant (ms)	0.11	±	0.02	0.19	±	0.03	0.13	±	0.02	0.10	±	0.01	0.16	±	0.03	(3:43)2.00, 0.13
Rheobase (mA)	8.53	±	2.55	6.47	±	2.89	6.50	±	1.76	6.54	±	1.16	9.35	±	1.96	(3:43)0.22, 0.88
Relative Refractory Period RRP (ms)	4.40	±	0.37	3.30	±	0.16	2.83	±	0.17*	2.55	±	0.13**	3.67	±	0.30	(3:48)8.61, < 0.01
Refractoriness at 2 ms (%)	76.61	±	21.07	50.58	±	18.13	42.74	±	21.28	45.44	±	21.86	44.03	±	5.21	(3:48)0.57, 0.64
Refractoriness at 2.5 ms (%)	30.43	±	5.63	18.69	±	5.96	10.47	±	7.16*	3.19	±	3.91**	19.46	±	4.29	(3:48)5.39, < 0.01
Superexcitability at 5 ms (%)	−6.61	±	1.92	−14.04	±	1.87	−16.20	±	1.18**	−19.00	±	1.180**	−10.83	±	2.30	(3:48)11.56, < 0.01
Superexcitability at 7 ms (%)	−11.04	±	1.72	−16.74	±	1.86	−18.01	±	1.27	−20.25	±	1.22**	−14.64	±	2.11	(3:48)7.31, < 0.01
Depolarisation TEd (90–100 ms)	34.86	±	1.81	32.48	±	4.11	32.26	±	3.04	32.33	±	2.86	35.96	±	2.33	(3:47)0.27, 0.85
Hyperpolarisation TEh (90–100 ms)	−73.57	±	6.79	−72.99	±	9.23	−68.42	±	5.44	−85.15	±	19.30	−108.79	±	32.65	(3:47)0.27, 0.85

Electrical excitability parameters determined for myelinated axons in human sural nerve in vitro before (Baseline) and during bath application of the Kv7 channel activator flupirtine (3-30 μM) and Kv7 channel blocker XE991 (10 μM). Data were analysed by one-way-ANOVA (rightmost column) and differences for individual groups relative to baseline were determined with post-hoc Tukey-Kramer tests with the levels of significance indicated in each column as * for p < 0.05 and for p < 0.01 respectively. Flupirtine reduced the RRP, the refractoriness at 2.5 ms, the magnitude of post-spike superexcitability at 5 ms and at 7 ms in a concentration-dependent manner but had no effect on the de- and hyperpolarizing threshold electrotonus.

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