O ß-hidroxibutirato modifica os processos de ativação e inativação dos canais para sódio e potássio em corpos celulares de neurônios dos gânglios das raizes dorsais de ratos.

Abstract

Under physiological conditions, the ketone bodies -hydroxybutyrate,acetoacetate and acetone are products of -oxidation of fatty acids that occurs in hepatocytes in response to hypoglycemia. This process occurs during fasting, high fat diets (such as the ketogenic diet, used in cases of drug-resistant epilepsy) and during diabetes mellitus in order to meet the energy requirements of some cell types, especially neurons. Considering the well-described sucess of ketogenic diets in the treatment of epilepsy and that most explainations of these effects point to metabolic effects on cell signalling that modify the activity of ATP-sensitive K+ channels, an electrophysiological approach could contribute to a better understanding of the actions of these substances on excitable cells. In this work, the stimulated Na+- and K+-ion currents were recorded in neurons from the dorsal root ganglia of adult Wistar rats, using the whole-cell configuration of the patch-clamp technique, in order to test the hypothesis that-hydroxybutyrate exerts acute effects on voltage-gated ion channels. Theresults show that the -hydroxybutyrate both increased the density of Na+currents, and shifted the midpoint of the activation and inactivation processes to more hyperpolarized values. However, when the cells were previously incubated with tetrodotoxin, we observed no effect on these parameters. The total K+ currents in DRGs can be divided into three components accordingly its voltage dependence, and activation/inactivation kinectics: IK, is an ohmic current; IAS, presents slow activation and inactivation kinectics and hyperpolarized midpoint of inactivation; IAF, presents fast activation and inactivation kinectics and depolarized midpoint of inactivation. The currents were stimulated using three protocols with distinct pre-pulses, and isolated using subtraction procedures. The analysis of the effects of -hydroxybutyrate on the currents showed no significant effects on IK. On the other hand, -hydroxybutyrate significantly reduced the current density of the IAF component, but not the IAs component. In addition, both the IAS as for the IAF current, caused dual effect (inverted J shaped curve) on the midpoint of the activation and inactivation processes. The effects of -hydroxybutyrate on Na+ and K+ currents were reversible upon washout.