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Kinetic analysis of developmental changes in vesicular monoamine transporter‐2 function
Author(s) -
Volz Trent J.,
Hanson Glen R.,
Fleckenstein Annette E.
Publication year - 2006
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20321
Subject(s) - monoamine neurotransmitter , methamphetamine , vesicle , chemistry , synaptic vesicle , medicine , endocrinology , vesicular monoamine transporter 2 , synapse , dopamine , transporter , dopamine transporter , biology , neuroscience , dopaminergic , biochemistry , receptor , serotonin , membrane , gene
The vesicular monoamine transporter‐2 (VMAT‐2) sequesters cytoplasmic dopamine (DA) into vesicles and may thus protect neurons from DA‐associated oxidative damage. VMAT‐2 function, as assessed by measuring [ 3 H]DA uptake, is less in adolescent when compared with young adult rats and VMAT‐2 susceptibility to methamphetamine also changes with age. Thus, developmental alterations in VMAT‐2 function warrant further investigation. The current study extends these findings by showing that the initial velocities of both DA uptake and methamphetamine‐induced DA efflux are less in adolescent postnatal day (PND 38–42) vs. young adult (PND 88–92) rats as assessed in nonmembrane associated (presumably cytoplasmic) vesicles purified from rat striatal synaptosomes. The decrease in DA uptake velocities is due to a decrease in the V max of DA uptake with no change in the K m . The density of kinetically active VMAT‐2 and VMAT‐2 immunoreactivity are less in adolescent vs. young adult rats while both the turnover number (2.4–2.8 s − 1 ) and rate constant for the association of DA with VMAT‐2 (˜ 1 × 10 7 M − 1 s − 1 ) are similar in these age groups. These results suggest that the kinetics of DA binding and translocation across the membrane are unaltered in the vesicles of PND 38–42 vs. PND 88–92 rats. However, decreased VMAT‐2 density in PND 38–42 rats reduces V max , which in turn lowers DA uptake. Synapse 60:474–477, 2006. © 2006 Wiley‐Liss, Inc.