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Updated: Oct 3, 2026
Whole-cell Patch-clamp Recordings from Morphologically- and Neurochemically-identified Hippocampal Interneurons
Published on: September 30, 2014
Blocking effect of intraperitoneal injection of phenylalanine on high-threshold calcium currents in rat hippocampal
A E Martynyuk1, S Savina, G G Skibo
1Bogomoletz Institute of Physiology, Ukrainian Academy of Sciences, Kiev, U.S.S.R.
Insights
Phenylalanine in rats with phenylketonuria decreased high-threshold calcium currents in brain cells. L-tyrosine supplementation restored these calcium currents, suggesting a potential therapeutic target for phenylketonuria.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Phenylketonuria (PKU) is a genetic disorder characterized by the inability to metabolize phenylalanine.
- Elevated phenylalanine levels induce neurochemical changes in the brain, potentially affecting neuronal function.
- Calcium channels play a critical role in neuronal excitability and neurotransmitter release.
Purpose of the Study:
- To investigate the impact of L-phenylalanine-induced phenylketonuria on calcium currents in rat hippocampal neurons.
- To determine the effect of L-tyrosine supplementation on these altered calcium currents.
Main Methods:
- Primary hippocampal neuron cultures were established from one-day-old rats.
- Rats received intraperitoneal injections of L-phenylalanine to model phenylketonuria.
- Whole-cell patch-clamp electrophysiology was used to record calcium currents.
- L-tyrosine was added to the culture medium for some experimental groups.
Main Results:
- L-phenylalanine-affected neurons showed no significant change in low-threshold calcium current amplitude.
- A significant decrease in high-threshold calcium current amplitude was observed in L-phenylalanine-treated neurons.
- Addition of L-tyrosine to the culture medium partially restored the high-threshold calcium current amplitude.
Conclusions:
- Phenylalanine-induced phenylketonuria selectively impairs high-threshold calcium channel function in hippocampal neurons.
- Tyrosine may counteract the detrimental effects of phenylalanine on these channels.
- These findings suggest a potential mechanism for brain dysfunction in phenylketonuria and highlight the role of tyrosine in modulating calcium channel activity.
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 Vt = +20 mV became 40 +/- 30% as contrasted to 416 +/- 130% in neurones from control animals (the amplitude of the calcium currents at Vt = -10 mV taken as 100%). The decrease remained during the whole time of culturing. Addition of L-tyrosine to the cultivation medium (50 microM) 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.
