Inhibition of sodium current by carbamazepine in dorsal root ganglion neurons in vitro.

Carbamazepine (CBZ), one of the most commonly prescribed antiepileptic drug, is proposed to inhibit Na+ channel. In this study, we have investigated the effects of CBZ on Na+ current, evoked in cultured dorsal root ganglion (DRG) neurons from neonatal rats using whole cell patch clamp technique. In small DRG neurons (20–25 μm), Na+ current was obtained by blocking K+ and Ca2+ currents with appropriate ion replacement and channel blockers. Separation of the Na+ current components was achieved on the basis of response to the conditioning voltage. The CBZ depressed Na+ current in a dose-dependent manner. The maximal Na+ current was depressed at 300 μM of CBZ, where 94±5.1% of depression was observed. The depression of normalized current amplitude was found to be 72±13.2%, 84±10%, 85±7.1% and 95±5.2% at 10, 30, 100 and 300 μM of CBZ concentrations, respectively, at –20 mV test pulse, when compared with control. The depression of current amplitude was observed as 48±12.3%, 42±15.2%, 71±17.7% and 90±5.8% at 10, 30, 100 and 300 μM of CBZ concentration, respectively, at 0 mV voltage pulse. The depression of Na+ currents was found to be dose-dependant at –20 and –10 mV but not at 0 mV. It is concluded that the depression of Na+ currents by CBZ may be responsible for inhibiting the neurotransmitter release.

Ptychodiscus brevis toxin decreases the spontaneous activity of rat right atria involving muscarinic receptors and potassium channels.

Marine dinoflagellate Ptychodiscus brevis toxin (PbTx), is known to produce toxic effects on cardiovascular system. The present experiments were conducted to evaluate the effect of synthetic phosphorus containing Ptychodiscus brevis toxin on spontaneously beating right atrium in vitro. The PbTx (0.84-84 microM) decreased the rate and force of right atrial contractions in a concentration-dependent manner. Ethanol, a vehicle present in highest concentration of PbTx, had no effect on atrial rate or force of contraction. Pretreatment with atropine blocked the PbTx-induced decrease in atrial rate and force of contraction. The tetraethylammonium, a potassium channel blocker, blocked the PbTx-induced decrease in atrial rate and force, where as, L-type of calcium channel blocker, nifedipine blocked the PbTx-induced force of contraction but not the rate changes. The results indicate that the PbTx decreased the atrial rate and force of contraction via cholinergic receptors involving K+ channel.