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Fig. 5 | The Journal of Headache and Pain

Fig. 5

From: Late sodium current blocker GS967 inhibits persistent currents induced by familial hemiplegic migraine type 3 mutations of the SCN1A gene

Fig. 5

Incorporation of GS967 binding and persistent current in a Hodgkin-Huxley type model of Na+ channel gating. GS967 is assumed to bind exclusively to the inactivated state with association rate constant λ [GS967] and dissociation rate constant μ (a). The values (λ = 10 μM− 1 s− 1, μ = 1 s− 1) were chosen (but not optimized in any systematic manner) to reproduce in a qualitative manner the kinetic onset of GS967 binding during a prolonged depolarization, and to qualitatively reproduce the kinetics of recovery from inactivation. Predictions of the model in response to typical IV protocol are shown in B and C for channel with no persistent currents (“WT”) and in D and E for a channel with 5% persistent currents without (b, d) or with 5 μM GS967 (c, e). Panels E shows simulated results for the indicated conditions for the recovery from inactivation at − 90 mV (symbols) overlaid with single exponentials fits (without GS967) and double exponential fits (with GS967), respectively

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