Canais iônicos na epilepsia : aspectos fisiopatológicos e terapêuticos
Several decades have been devoted to study of epilepsy pathophysiology, but the knowledge in the area contributed to only a partial understanding of the mechanisms involved. Data from the World Health Organization indicate a epilepsy worldwide prevalence in about 50 million people. In Brazil, studies on the epilepsy epidemiological aspects are scarce, however, based on the latest census and worldwide prevalence, it is assumed that almost 2 million people are affected by the disease in the country. An epileptic seizure is a period of abnormal synchronous excitation of a neuronal population. The balance between control systems that prevent neurons from a excessive action potential discharge and other systems that facilitate excitation maintains the proper functioning of the central nervous system. Ion channels are involved in the process of neurons excitability and communication between them through the release of neurotransmitters, however, only recently has direct evidence of the importance of channels dysfunctions in natural emergence of this neuronal disorder. The genetic investigations led some epileptic syndromes were considered channelopathies and therefore increased the understanding of convulsive disorders pathophysiology. The epileptic channelopathies are caused by mutations in genes encoding ion channels, either voltage-gated ion channels (Na+, K+, Ca2 + and Cl-) as ligand-gated ion channels, such as nicotinic acetylcholine receptors (nAChR) and ionotropic gamma-aminobutyric acid receptors (GABAA). Generally, these mutations cause changes in channels electrophysiological properties leading to increased excitability or decreased inhibition. This imbalance in functioning of neural networks leads to seizures appearance, which is the most outstanding clinic manifestation of epilepsy. The antiepileptic drugs act on multiple molecular targets modulating the activity of voltage-sensitive ion channels (Na+ and Ca2+ channel inhibitors and K+ channel activators), increasing GABAA receptors-mediated neuronal inhibition (GABAergic modulators and drugs that increase the GABA availability) or decreasing synaptic excitation (glutamate receptor antagonists). The biophysical modifications in channels behavior that are induced by antiepileptic drugs are often opposite to the effects generated by mutations. However, given the inability to cure of currently available antiepileptic drugs, the major challenge for scientific research is the discovery of a treatment capable of prevent or reverse epilepsy.
Crise epiléptica, Canais iônicos, Canalopatias
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