Overview
- Belardinelli, L., et al. (2013) J. Pharmacol. Exp. Ther. 344, 23.
It is recommended to prepare fresh solutions before use.
Centrifuge all products before use (10000 x, g 5 min). Avoid multiple freezing and thawing.
Alomone Labs GS967 inhibits peak and late INa current of NaV1.5 channels heterologously expressed in Xenopus oocytes.A. Representative time course of GS967 (#G-225) action. Membrane potential was held at -100 mV, current was elicited by a 100 ms voltage step to -10 mV every 10 sec.
5 µM GS967 (green) inhibited NaV1.5 peak and late INa current.
B. Superimposed traces of NaV1.5 current after application of control (black) and 5 µM GS967 (green) taken from the recording in A.
Alomone Labs GS967 inhibits ATX-II evoked current of NaV1.5 channels (late INa) heterologously expressed in Xenopus oocytes.A. Representative time course of GS967 (#G-225) action. Normalized current area was plotted as a function of time. Holding potential was -100 mV and currents were stimulated every 10 seconds by a voltage step of 100 ms from holding potential to 0 mV. 5 μM GS967 (magenta) inhibited the late INa induced by 200 nM ATX-II (green).
B. Superimposed traces of NaV1.5 current after application of control (black), 200 nM ATX-II (green) and 200 nM ATX-II + 5 µM GS967 (magenta) taken from the recording in A.
- Yu, F.H. et al. (2003) Gen. Biol., 4, 207.
- Mulcahy, V. et al. (2019) J. Med. Chem., 62, 8695.
- Makielski, J.C. (2009) J. Cardiovasc. Pharmacol., 54, 279.
- Belardinelli, L. et al. (2013) J. Pharmacol. Exp. Ther., 344, 23.
- Del Canto, I. et al. (2018) Cardiovasc. Drugs. Ther., 32, 413.
- Baker, M.E. et al. (2018) Epilepsia. 59, 1166.
Voltage-gated sodium (NaV) channels are integral membrane proteins that play an essential role in the regulation of action potentials in neurons, myocytes and endocrine cells1. Given their central role in electrical signaling, NaVs inhibitors have been extensively studied. Inhibitors of Navs have been found to be highly effective as local anesthetics, anticonvulsants and antiarrhythmic and in the prevention of myocardial ischemia and heart failure2.
Late Na+ current (INaL) is a phenomenon that occurs when NaVs in myocytes fail to regulate Na+ influx. Increased magnitude of late INaL is associated with pathological conditions. Inhibition of cardiac late INa is a strategy to suppress arrhythmias and Na+-dependent calcium overload associated with myocardial ischemia and heart failure3.
GS967 is a potent and selective inhibitor of late INa. It was shown to inhibit ATX-II (#STA-700) induced late INa in ventricular myocytes and isolated hearts4-5.
Photogenic variant SCN8A, encoding the NaV α subunit Nav1.6, is a known cause of epilepsy. Treatment of mice carrying the SCN8A mutation with G967 resulted in lower seizure burden and complete protection from seizure‐associated lethality6.
GS967 (#G-225) is a highly pure, synthetic, and biologically active compound.
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