Blocking effect of intraperitoneal injection of phenylalanine on high-threshold calcium currents in rat hippocampal neurones

Abstract

Calcium currents were recorded in cultured (5–7 days) hippocampal neurones isolated from one-day-old rats. The animals obtained intraperitoneal injections of l-phenylalanine which induces in the brain biochemical changes characteristic of phenylketonuria. It has been found that the amplitude of the low-threshold calcium current in l-phenylalanine-affected neurones was not appreciably changed compared with that in neurones from control (non-injected) animals. However, the amplitude of the high-threshold calcium current was essentially decreased. Its relative amplitude at V t = +20 mV became 40 ± 30% as contrasted to 416 ± 130% in neurones from control animals (the amplitude of the calcium currents at V t = −10 mV taken as 100%). The decrease remained during the whole time of culturing. Addition of l-tyrosine to the cultivation medium (50 μM) restored the high-voltage calcium current, its relative amplitude reaching 280 ± 57%. The data are discussed in conjunction with the previously obtained results about antagonistic modulatory action of tyrosine and phenylalanine on the functioning of high-threshold calcium channels and possible mechanisms of brain dysfunction during phenylketonuria.