Effects of Essential Fatty Acids on Voltage-Regulated Ionic Channels and Seizure Thresholds in Animals

If polyunsaturated fatty acids (PUFAs) have an antiarrhythmic action on the heart, do they also have a suppressant action on other excitable cells, such as neuronal tissue? The answer to this question is important, because there are several conditions where lowering of neuronal excitability obviously has a beneficial effect and where there is still a need for new and better treatments. Neuropathic pain and neurological disorders such as epilepsy are two examples. The work of Leaf and co-workers (Leaf, Kang, Xiao, Billman & Voskuyl, 1999a; Leaf, Kang, Xiao, Billman & Voskuyl, 1999b) has convincingly demonstrated that the stabilizing effect of PUFAs on the electrical activity of isolated cardiac myocytes stems mainly from inhibition of voltage-regulated sodium and calcium currents. Some studies in neuronal preparations have pointed in the same direction (Park & Ahmed, 1992; Takenaka, Horie & Hori, 1987; Takenaka, Horie, Hori & Kawakami, 1988). In this respect, PUFAs bear a striking resemblance to local anesthetics and a number of antiepileptic drugs. Furthermore, one of the antiepileptic drugs that interact with sodium channels, valproic acid, is actually a short-chain fatty acid. This remarkable coincidence prompted us to investigate the possible antiepileptic action of a number of PUFAs on isolated hippocampal neurons and in an experimental epilepsy model in vivo. The second reason why PUFAs deserve interest in the context of epilepsy is the recent re-emergence of the ketogenic diet as an alternative for antiepileptic drug treatment. The diet has a high fat content and is low in carbohydrates. Although it does not seem to work in all patients, it has been remarkably successful in treating, in particular, the most difficult types of epilepsy in children. At present, it is unclear why and how the diet works, but it is not unreasonable to suppose that the composition of the diet and the different fat components should have an influence. This subject is discussed in detail in Chapter 17.