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Neuronal T-type voltage-gated Ca(2+) channels are reported to have physiological roles that include regulation of burst firing, Ca(2+) oscillations, and neurotransmitter release. These roles are often exposed experimentally by blocking T-type channels with micromolar Ni(2+). We used Ni(2+) to explore the role of axonal T-type channels in dopamine (DA) release in mouse striatum, but identified significant off-target effects on DA uptake. Ni(2+) (100 μM) reversibly increased electrically evoked DA release and markedly extended its extracellular lifetime, detected using fast-scan cyclic voltammetry. Prior inhibition of the DA transporter (DAT) by cocaine (5 μM) occluded the facilitatory action of Ni(2+) on DA release and conversely, allowed Ni(2+) to inhibit release, presumably through T-channel inhibition. Ni(2+) further prolonged the timecourse of DA clearance suggesting further inhibition of DA uptake. In summary, Ni(2+) has major effects on DA transmission besides those due to T-channels that likely involve inhibition of the DAT.

Original publication

DOI

10.1021/cn500274g

Type

Journal article

Journal

ACS Chem Neurosci

Publication Date

21/01/2015

Volume

6

Pages

124 - 129

Keywords

Dopamine, Ni2+, T-type VGCC, dopamine transporter, voltammetry, Acetylcholine, Action Potentials, Analysis of Variance, Animals, Biophysics, Calcium Channel Blockers, Calcium Channels, T-Type, Corpus Striatum, Dihydro-beta-Erythroidine, Dopamine, Dopamine Agents, Dose-Response Relationship, Drug, Electric Stimulation, Electrochemical Techniques, In Vitro Techniques, Male, Mice, Mice, Inbred C57BL, Neurons, Nickel