Long-term fish oil supplementation attenuates seizure activity in the amygdala induced by 3-mercaptopropionic acid in adult male rats.

Several studies have provided evidence of significant effects of omega-3 fatty acids on brain functionality, including seizures and disorders such as epilepsy. Fish oil (FO) is a marine product rich in unsaturated omega-3 fatty acids. Considering that the amygdala is one of the brain structures most sensitive to seizure generation, we aimed to evaluate the effect of long-term chronic FO supplementation (from embryonic conception to adulthood) on the severity of seizures and amygdaloid electroencephalographic activity (EEG) in a 3-mercaptopropionic acid (3-MPA)-induced seizure model using adult rats. Female Wistar rats were fed a commercial diet supplemented daily with FO (300mg/kg) from puberty through mating, gestation, delivery, and weaning of the pups. Only the male pups were then fed daily with a commercial diet supplemented with the same treatment as the dam up to the age of 150days postpartum, when they were bilaterally implanted in the amygdala to record behavior and EEG activity before, during, and after seizures induced by administering 3-MPA. Results were compared with those obtained from rats supplemented with palm oil (PO) and rats treated with a vehicle (CTRL). The male rats treated with FO showed longer latency to seizure onset, fewer convulsive episodes, and attenuated severity compared those in the PO and CTRL groups according to the Racine scale. Moreover, long-term FO supplementation was associated with a reduction of the absolute power (AP) of the fast frequencies (12-25Hz) in the amygdala during the seizure periods. These findings support the idea that chronic supplementation with omega-3 of marine origin may have antiseizure properties as other studies have suggested.

Blockade of currents by the antimalarial drug chloroquine in feline ventricular myocytes.

The effects of the antimalarial drug chloroquine on cardiac action potential and membrane currents were studied at clinically relevant concentrations. In cat Purkinje fibers, chloroquine at concentrations of 0.3 to 10 microM increased action potential duration, and reduced maximum upstroke velocity. At concentrations of 3 and 10 microM, chloroquine increased automaticity and reduced maximum diastolic potential, and after 60 min of perfusion with a concentration 10 microM, spontaneous activity was abolished. In isolated cat ventricular myocytes, chloroquine also increased action potential duration in a concentration-dependent manner, and reduced resting membrane potential at 3 and 10 microM. In voltage-clamped cat ventricular myocytes, chloroquine blocked several inward and outward membrane currents. The order of potency was inward rectifying potassium current (I(K1)) > rapid delayed rectifying potassium current (I(Kr)) > sodium current (I(Na)) > L-type calcium current (I(Ca-L)). Only tonic block of I(Na) and I(Ca-L) was observed at a stimulation frequency of 0.1 Hz and no additional blockade was observed during stimulation trains applied at 1 Hz. The effect of chloroquine on I(K1) was voltage-dependent, with less pronounced blockade at negative test potentials. In addition, unblock was achieved by hyperpolarizing pulses to potentials negative to the current reversal potential. Chloroquine blocked the rapid component of the delayed rectifying outward current, I(Kr,) but not the slow component, I(Ks). These findings provide the cellular mechanisms for the prolonged QT interval, impaired ventricular conduction, and increased automaticity induced by chloroquine, which have been suggested as responsible for the proarrhythmic effects of the drug.

Chloroquine blocks the background potassium current in guinea pig atrial myocytes.

In this study we examined the effects of chloroquine on the muscarinic potassium current, I(K-ACh), and the inward rectifying potassium current, I(K1). We utilized three ways to induce I(K-ACh): activating the M2-muscarinic receptors with carbachol, activating the purinergic A1-receptors with adenosine and directly activating the G(K)-protein coupled with these receptors in an irreversible way with GTPgammaS. In experiments using the whole-cell configuration of the patch-clamp technique, we found that chloroquine, independently from the manner of activation of I(K-ACh), was able to block this current with similar potency. These results strongly suggest that chloroquine may be acting directly on the muscarinic potassium channel. Chloroquine also blocked I(K1) with similar potency, in both guinea pig atrial and ventricular myocytes.