Class Ic antiarrhythmics block human skeletal muscle Na channel during myotonia-like stimulation

Aoike, Futoshi; Takahashi, Masanori; Sakoda, Saburo

doi:10.1016/j.ejphar.2005.12.021

Cited by 11 publications

(9 citation statements)

References 27 publications

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“…The pipette solution contained (in mM) NaF 10, CsF 110, CsCl 20, EGTA 10, and HEPES 10 (pH 7.35 adjusted with CsOH). After testing apamin 500 nM, fleicainide 100 µM was used as a positive control [26]. For measuring I Ca , we replaced extracellular calcium with barium to lessen the rundown phenomenon [27], [28].…”

Section: Methodsmentioning

confidence: 99%

Apamin Does Not Inhibit Human Cardiac Na+ Current, L-type Ca2+ Current or Other Major K+ Currents

Weiss

et al. 2014

PLoS ONE

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BackgroundApamin is commonly used as a small-conductance Ca2+-activated K+ (SK) current inhibitor. However, the specificity of apamin in cardiac tissues remains unclear.ObjectiveTo test the hypothesis that apamin does not inhibit any major cardiac ion currents.MethodsWe studied human embryonic kidney (HEK) 293 cells that expressed human voltage-gated Na+, K+ and Ca2+ currents and isolated rabbit ventricular myocytes. Whole-cell patch clamp techniques were used to determine ionic current densities before and after apamin administration.ResultsCa2+ currents (CACNA1c+CACNB2b) were not affected by apamin (500 nM) (data are presented as median [25th percentile;75th percentile] (from –16 [–20;–10] to –17 [–19;–13] pA/pF, P = NS), but were reduced by nifedipine to –1.6 [–3.2;–1.3] pA/pF (p = 0.008). Na+ currents (SCN5A) were not affected by apamin (from –261 [–282;–145] to –268 [–379;–132] pA/pF, P = NS), but were reduced by flecainide to –57 [–70;–47] pA/pF (p = 0.018). None of the major K+ currents (I Ks, I Kr, I K1 and I to) were inhibited by 500 nM of apamin (KCNQ1+KCNE1, from 28 [20]; [37] to 23 [18]; [32] pA/pF; KCNH2+KCNE2, from 28 [24]; [30] to 27 [24]; [29] pA/pF; KCNJ2, from –46 [–48;–40] to –46 [–51;–35] pA/pF; KCND3, from 608 [505;748] to 606 [454;684]). Apamin did not inhibit the I Na or I CaL in isolated rabbit ventricular myocytes (I Na, from –67 [–75;–59] to –68 [–71;–59] pA/pF; I CaL, from –16 [–17;–14] to –14 [–15;–13] pA/pF, P = NS for both).ConclusionsApamin does not inhibit human cardiac Na+ currents, L-type Ca2+ currents or other major K+ currents. These findings indicate that apamin is a specific SK current inhibitor in hearts as well as in other organs.

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Section: Methodsmentioning

confidence: 99%

Apamin Does Not Inhibit Human Cardiac Na+ Current, L-type Ca2+ Current or Other Major K+ Currents

Weiss

et al. 2014

PLoS ONE

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“…In this study, the proband did not have any symptom relief with mexiletine, oxcarbazepine, or thiazide diuretics. Although flecainide has been shown to be an effective hNav1.4 channel blocker in vitro [2, 8, 9], its clinical use as an antimyotonic agent is rarely reported [10]. The improvement of myotonia by flecainide obtained here suggests that there may be a relationship between the G1306E mutation and the response to flecainide therapy.…”

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confidence: 75%

Dramatic improvement of myotonia permanens with flecainide: a two-case report of a possible bench-to-bedside pharmacogenetics strategy

Desaphy

Modoni

LoMonaco

et al. 2012

Eur J Clin Pharmacol

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“…35 The clinical efficacy of flecainide (therapeutic concentrations of 0.4-2 μM), 36 was attributed to its UDB of peak hNa v 1.4 I Na at a HP of -90 mV at a frequency of 50 Hz (IC 50 of 3.1 μM). 37 However, longterm management of myotonic episodes by either mexiletine or flecainide is limited due to their cardiovascular and CNS-related side-effects. 15 It is important to note that flecainide has a very narrow therapeutic index and can exhibit toxicity at therapeutic concentrations.…”

confidence: 99%

Ranolazine block of human Na_v1.4 sodium channels and paramyotonia congenita mutants

El-Bizri¹,

Kahlig²,

Shyrock³

et al. 2011

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Class Ic antiarrhythmics block human skeletal muscle Na channel during myotonia-like stimulation

Cited by 11 publications

References 27 publications

Apamin Does Not Inhibit Human Cardiac Na+ Current, L-type Ca2+ Current or Other Major K+ Currents

Apamin Does Not Inhibit Human Cardiac Na+ Current, L-type Ca2+ Current or Other Major K+ Currents

Dramatic improvement of myotonia permanens with flecainide: a two-case report of a possible bench-to-bedside pharmacogenetics strategy

Ranolazine block of human Na_v1.4 sodium channels and paramyotonia congenita mutants

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Class Ic antiarrhythmics block human skeletal muscle Na channel during myotonia-like stimulation

Cited by 11 publications

References 27 publications

Apamin Does Not Inhibit Human Cardiac Na+ Current, L-type Ca2+ Current or Other Major K+ Currents

Apamin Does Not Inhibit Human Cardiac Na+ Current, L-type Ca2+ Current or Other Major K+ Currents

Dramatic improvement of myotonia permanens with flecainide: a two-case report of a possible bench-to-bedside pharmacogenetics strategy

Ranolazine block of human Nav1.4 sodium channels and paramyotonia congenita mutants

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Ranolazine block of human Na_v1.4 sodium channels and paramyotonia congenita mutants