Neurochemical characterization of the striatum and the nucleus accumbens in L-type Ca(v)1.3 channels knockout mice.
L-type Ca(v)1.3 channels control the autonomous pacemaking of the substantia nigra (SN) dopamine (DA) neurons, which maintains the sustained release of DA in the striatum, its target structure. The persistent engagement of L-type channels during pacemaking might lead to increased vulnerability to environmental stressors or degenerative processes, providing a mechanism for the development of Parkinson's disease (PD). Interestingly, L-type channels are not necessary for pacemaking, opening the possible use of calcium channel antagonists as neuroprotective agents for PD without disturbing normal DA function. In this study we aimed to evaluate the consequences of Ca(v)1.3 channels deletion at the neurochemical level. For this purpose, tissue concentrations of DA and their respective metabolites were measured using high performance liquid chromatography (HPLC) in the striatum and the nucleus accumbens (NAcc) of mice lacking the gene for the Ca(v)1.3 channel subunit (CACNA1D) and compared to those in wild-type mice. Striatal DA level did not differ between the two groups. In contrast, the level of serotonin, glutamate, GABA, and taurine were increased by more than 50% in the striatum of Ca(v)1.3 null mice. Neurotransmitters levels in the NAcc did not differ between the different groups. In conclusion, our results neurochemically corroborate the robustness of the nigrostriatal DA neurons in the absence of Ca(v)1.3 channels, but suggest that complete deletion of this channel affected a variety of other transmitter systems.
Department of Neurology, Campus Virchow, Charité University Medicine, Berlin, Germany.
Ferry S P
FS
Sagala
Daniel
D
Harnack
Evgeny
E
Bobrov
Reinhard
R
Sohr
Christoph
C
Gertler
D
D
James Surmeier
Andreas
A
Kupsch
D000818:Animals; D020746:Calcium Channels, L-Type / Q000235:genetics* / Q000502:physiology*; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D004298:Dopamine / Q000378:metabolism; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009714:Nucleus Accumbens / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D012701:Serotonin / Q000378:metabolism; D013654:Taurine / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
C485995:Cacna1d protein, mouse; D020746:Calcium Channels, L-Type; D013654:Taurine; D012701:Serotonin; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D004247:DNA; D004298:Dopamine