A glutathione deficit alters dopamine modulation of L-type calcium channels via D2 and ryanodine receptors in neurons

Free Radical Biology & Medicine
Pascal SteulletKim Q Do

Abstract

Synthesis of glutathione, a major redox regulator, is compromised in schizophrenia. We postulated that the resulting glutathione deficit via its effect on redox-sensitive proteins could contribute to dysfunction of some neurotransmitter systems in schizophrenia. We investigated whether a glutathione deficit, induced by a blocker of glutathione synthesis, L-buthionine-(S,R)-sulfoximine, affects intracellular pathways implicated in dopamine signaling in neurons, namely dopamine modulation of calcium responses to NMDA. Such a glutathione deficit changed the modulation of responses by dopamine, from enhanced responses in control neurons (likely via D1-type receptors) to decreased responses in low-glutathione neurons (via D2-type receptors). This difference in dopamine modulation was due to a different modulation of L-type calcium channels activated during NMDA stimulation: dopamine enhanced function of these channels in control neurons but decreased it in low-glutathione neurons. The effect of a glutathione deficit on dopamine signaling was dependent on the redox-sensitive ryanodine receptors (RyRs), whose function was enhanced in low-glutathione neurons. This suggests that enhanced RyRs in low-glutathione neurons strengthens intra...Continue Reading

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Citations

Dec 4, 2010·Antioxidants & Redox Signaling·Jeffrey K Yao, Matcheri S Keshavan
Jun 2, 2009·Current Opinion in Neurobiology·Kim Q DoMichel Cuenod
Jan 12, 2016·Reviews in the Neurosciences·Ivan ZaletelNela Puškaš

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