- Rao, S. and Sikdar, S.K. (2000) Pflügers Arch. 439, 349.
- Alomone Labs Aconitine modulates native TTX-sensitive NaV channel currents in ND7/23 cells.NaV currents were elicited by a 50 ms voltage ramp from the holding potential of -100 mV to +60 mV, applied every 10 sec using whole-cell voltage clamp. A. Time course of current at -20 mV (black) and -30 mV (green) along the voltage ramp, showing the effect of 0.8 μM Aconitine (#A-150) application (horizontal bar) on current voltage dependence. B. Superimposed traces of NaV currents in ND7/23 cells under control conditions and after 6 min perfusion with 0.8 μM Aconitine (as indicated).
Voltage-gated sodium channels (NaV) are present in most excitable cell membranes and play an important role in generating action potentials. A variety of toxins and chemicals are known to either block or modulate Na+ channels and have proven to be invaluable in investigating the physiological characteristics of these channels1. Most notably, tetrodotoxin (TTX), a potent and selective blocker of Na+ channels, binds to neurotoxin receptor site 1 to block them2.
Aconitine is a diterpense two-ester alkaloid derived from the tubers of aconitinum plants and has been used as traditional herbal medicine in China and Japan since ancient times. Modern pharmacological studies have shown that aconitine has effects of analgesia and anesthesia, anti-inflammatory, immune regulation, anti-tumor and cardiotonic actions3,4. Concurrently, aconitine also presents enormous toxicity5. It is well known for its toxic effects on the heart and central nervous system where it causes cardiac arrhythmias, systemic paralysis and coma6. Aconitine alters the kinetics and voltage dependence of Na+ channel activation, inhibits Na+ channel inactivation through binding to neurotoxin receptor site 2 and causes persistent activation of Na+ channels at the resting membrane potential7.