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Limited regulation of somatodendritic dopamine release by voltage‐sensitive Ca 2+ channels contrasted with strong regulation of axonal dopamine release
Author(s) -
Chen Billy T.,
Moran Kimberly A.,
Avshalumov Marat V.,
Rice Margaret E.
Publication year - 2006
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.1471-4159.2005.03519.x
Subject(s) - dopamine , chemistry , autoreceptor , substantia nigra , striatum , channel blocker , ionotropic effect , pars compacta , voltage dependent calcium channel , calcium channel , glutamate receptor , biophysics , neuroscience , pharmacology , calcium , agonist , receptor , biology , biochemistry , dopaminergic , organic chemistry
The mechanism underlying somatodendritic release of dopamine (DA) appears to differ from that of axon‐terminal release. Specifically, somatodendritic DA release in the substantia nigra pars compacta (SNc) persists in low extracellular Ca 2+ concentrations that are insufficient to support axonal release in striatum, suggesting that limited Ca 2+ entry is necessary to trigger somatodendritic release. Here, we compared the role of voltage‐dependent Ca 2+ channels in mediating DA release in striatum versus SNc using specific blockers of N‐, P/Q‐, T‐, R‐ and L‐type Ca 2+ channels individually and in combination. Release of DA evoked by a single stimulus pulse in the dorsal striatum and SNc of guinea‐pig brain slices was monitored in real time using carbon‐fiber microelectrodes with fast‐scan cyclic voltammetry. Single‐pulse evoked DA release was shown to be independent of regulation by concurrently released glutamate or GABA acting at ionotropic receptors in both regions. Under these conditions, striatal DA release was completely prevented by an N‐type channel blocker, ω‐conotoxin GVIA (100 n m ), and was decreased by 75% by the P/Q‐type channel blocker ω‐agatoxin IVA (200 n m ). Blockade of T‐type channels with Ni 2+ (100 µ m ) or R‐type channels with SNX‐482 (100 n m ) decreased axonal release in striatum by 25%, whereas inhibition of L‐type channels with nifedipine (20 µ m ) had no effect. By contrast, none of these Ca 2+ ‐channel blockers altered the amplitude of somatodendritic DA release in the SNc. Even a cocktail of all blockers tested did not alter release‐signal amplitude in the SNc, although the duration of the release response was curtailed. The limited involvement of voltage‐dependent Ca 2+ channels in somatodendritic DA release provides further evidence that minimal Ca 2+ entry is required to trigger the release process, compared with that required for axon‐terminal release.