Hector Maldonado Lecture Channelopathies as a source of neurological disorders.

UCHITEL O.D.

Huerta Grande. Cordoba

Conferencia; XXVII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; 2012

Sociedad Argentina de Investigación en Neurociencias

Channelopathies as a source of neurological disorders Osvaldo Uchitel Instituto de Fisiologia, Biologia Molecular y Neurociencias. IFIBYNEUBA- CONICET, University of Buenos Aires, Buenos Aires, Argentina. During the past two decades it has become apparent that diseases once thought unrelated share alterations in the regulation of ion channels. Ion channels regulate neuronal and muscular excitability. Alterations in their function could result in conditions such as periodic paralysis, epilepsy and migraines. In these cases, the result of neurobiological research has led to the conclusion that the underlying cause is a channelopathy, which has served as guide for the development of therapies to treat these diseases. By way of example, many antiepileptic drugs block the sodium channel or the activation of ligand-dependent receptors. Migraine is one of the most common neurological conditions. However, there is a rarer form of migraine, the so called familial hemiplegic, which is accompanied by hemiparesis, and has a monogenic origin related to mutations of the P / Q calcium channel. The generation of transgenic mice with different human mutations (knock in) allowed the study, in their normal cellular environment and under their natural regulation, of the expression of the mutated channel and their effects on synaptic transmission. It has also made possible the detailed investigation on the effect of potential therapeutic agents. The results of these studies show that, at the synaptic level, the phenotypic expression of the mutation depends particularly on the kinetic properties of the action potential of neurons, generating a gain increase in the excitatory neurons but not in the inhibitory ones. This disparity leads to an imbalance between excitation and inhibition that could be the basis of the cortical hyperexcitability observed both in patients and in animal models. This phenomenon has been interpreted as the starting point of the aura, which precedes the migraine attack.