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Involvement of KCNQ2 subunits in [ 3 H]dopamine release triggered by depolarization and pre‐synaptic muscarinic receptor activation from rat striatal synaptosomes
Author(s) -
Martire Maria,
D’Amico Monia,
Panza Elisabetta,
Miceli Francesco,
Viggiano Davide,
Lavergata Francesco,
Iannotti Fabio Arturo,
Barrese Vincenzo,
Preziosi Paolo,
Annunziato Lucio,
Taglialatela Maurizio
Publication year - 2007
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.1471-4159.2007.04562.x
Subject(s) - chemistry , oxotremorine , depolarization , muscarinic acetylcholine receptor , dopamine , medicine , endocrinology , pirenzepine , agonist , receptor , biochemistry , biology
KCNQ2 and KCNQ3 subunits encode for the muscarinic‐regulated current (I KM ), a sub‐threshold voltage‐dependent K + current regulating neuronal excitability. In this study, we have investigated the involvement of I KM in dopamine (DA) release from rat striatal synaptosomes evoked by elevated extracellular K + concentrations ([K + ] e ) and by muscarinic receptor activation. [ 3 H]dopamine ([ 3 H]DA) release triggered by 9 mmol/L [K + ] e was inhibited by the I KM activator retigabine (0.01–30 μmol/L; E max = 54.80 ± 3.85%; IC 50 = 0.50 ± 0.36 μmol/L). The I KM blockers tetraethylammonium (0.1–3 mmol/L) and XE‐991 (0.1–30 μmol/L) enhanced K + ‐evoked [ 3 H]DA release and prevented retigabine‐induced inhibition of depolarization‐evoked [ 3 H]DA release. Retigabine‐induced inhibition of K + ‐evoked [ 3 H]DA release was also abolished by synaptosomal entrapment of blocking anti‐KCNQ2 polyclonal antibodies, an effect prevented by antibody pre‐absorption with the KCNQ2 immunizing peptide. Furthermore, the cholinergic agonist oxotremorine (OXO) (1–300 μmol/L) potentiated 9 mmol/L [K + ] e ‐evoked [ 3 H]DA release ( E max = 155 ± 9.50%; EC 50 = 25 ± 1.80 μmol/L). OXO (100 μmol/L)‐induced [ 3 H]DA release enhancement was competitively inhibited by pirenzepine (1–10 nmol/L) and abolished by the M 3 ‐preferring antagonist 4‐diphenylacetoxy N ‐methylpiperidine methiodide (1 μmol/L), but was unaffected by the M 1 ‐selective antagonist MT‐7 (10–100 nmol/L) or by Pertussis toxin (1.5–3 μg/mL), which uncouples M 2 ‐ and M 4 ‐mediated responses. Finally, OXO‐induced potentiation of depolarization‐induced [ 3 H]DA release was not additive to that produced by XE‐991 (10 μmol/L), was unaffected by retigabine (10 μmol/L), and was abolished by synaptosomal entrapment of anti‐KCNQ2 antibodies. Collectively, these findings indicate that, in rat striatal nerve endings, I KM channels containing KCNQ2 subunits regulate depolarization‐induced DA release and that I KM suppression is involved in the reinforcement of depolarization‐induced DA release triggered by the activation of pre‐synaptic muscarinic heteroreceptors.