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Na + /H + exchanger inhibition modifies dopamine neurotransmission during normal and metabolic stress conditions
Author(s) -
Rocha Marcelo A.,
Crockett David P.,
Wong LaiYoong,
Richardson Jason R.,
Sonsalla Patricia K.
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2008.05355.x
Subject(s) - dopamine , neurotransmission , striatum , substantia nigra , neurotoxin , chemistry , endocrinology , medicine , gene isoform , midbrain , neurotransmitter , biology , biochemistry , dopaminergic , central nervous system , receptor , gene
Na + /H + exchanger (NHE) proteins are involved in intracellular pH and volume regulation and may indirectly influence neurotransmission. The abundant NHE isoform 1 (NHE1) has also been linked to brain cell damage during metabolic stress. It is not known, however, whether NHE1 or other NHE isoforms play a role in striatal dopamine (DA) neurotransmission under normal or metabolic stress conditions. Our study tested the hypothesis that NHE inhibition with cariporide mesilate (HOE‐642) modifies striatal DA overflow and DAergic terminal damage in mice caused by the mitochondrial inhibitor malonate. We also explored the expression of NHE1–5 in the striatum and substantia nigra. Reverse microdialysis of HOE‐642 elicited a transient elevation followed by a reduction in DA overflow accompanied by a decline in striatal DA content. HOE‐642 pre‐treatment diminished the malonate‐induced DA overflow without reducing the intensity of the metabolic stress or subsequent DAergic axonal damage. Although NHE isoforms 1–5 are expressed in the striatum and midbrain, NHE1 protein was not co‐located on nigrostriatal DAergic neurons. The absence of NHE1 co‐location on DAergic neurons suggests that the effects of HOE‐642 on striatal DA overflow are either mediated via NHE1 located on other cell types or that HOE‐642 is acting through multiple NHE isoforms.