Calcium regulation in mouse mesencephalic neurons—Differential roles of Na+/Ca2+ exchanger, mitochondria and endoplasmic reticulum. Issue 6 (June 2016)

• Record Type: Journal Article
• Authors: Wu, Pei-Chun; Kao, Lung-Sen
• Is Part Of: Cell calcium. Volume 59:Issue 6(2016)
• Page Start: 299
• Page End: 311
• Publication Date: 2016-06
• Subjects: CCCP m-chlorophenylhydrazone -- DA neurons dopaminergic neurons -- ER endoplasmic reticulum -- [Ca2+]ER ER Ca2+ concentration -- GAD67 glutamate decarboxylase 67 -- [Ca2+]i intracellular Ca2+ concentration -- [Ca2+]MITO mitochondrial Ca2+ concentration -- NCX K+-dependent Na+/Ca2+ exchangers -- NCKX K+-independent Na+/Ca2+ exchangers -- non-DA neurons non-dopaminergic neurons -- PD Parkinson's disease -- TG thapsigargin -- TH tyrosine hydroxylase -- vGluT2 vesicular glutamate transporter -- VGCCs voltage-gated Ca2+ channels; Dopaminergic neurons -- Parkinson's disease -- Ca2+ -- Na+/Ca2+ exchanger -- Endoplasmic reticulum -- Mitochondria; Calcium -- Metabolism -- Periodicals; Vertebrates -- Physiology -- Periodicals; Calcium -- Physiological effect -- Periodicals; Cell physiology -- Periodicals; Calcium in the body -- Periodicals; 572.516
• DOI: 10.1016/j.ceca.2016.03.008
• Languages: English
• ISSNs: 0143-4160

Abstract

Graphical abstract: Highlights: Na + /Ca 2+ exchangers play prominent roles in removing [Ca 2+ ]i induced by glutamate but not depolarization in mesencephalic neurons. ER, functionally closer to K + -dependent Na + /Ca 2+ exchanger, is a Ca 2+ source which provide limited effects. Mitochondria act as the major Ca 2+ storages and functionally closer to K + -independent Na + /Ca 2+ exchanger. These three machineries cooperate interactively and behave similarly in the regulation of [Ca 2+ ]i in the mesencephalic neurons. Single-cell RT-PCR analysis suggests each individual neurons consist of different combinations of Na + /Ca 2+ exchangers subtypes. Abstract: Midbrain dopaminergic (DA) neurons are the key to finely tune the voluntary movement, habit and motivation. The progressive and selective degeneration of these neurons is a pathological hallmark of Parkinson's disease (PD). The susceptibility of DA neurons in the SNpc may result from differences in how Ca 2+ is handled. However, very little information is available about the mechanisms involved in the regulation of intracellular Ca 2+ concentration ([Ca 2+ ]i ) in DA neurons. In this study, the relative contributions of various Na + /Ca 2+ exchangers and their interplay with internal Ca 2+ stores, endoplasmic reticulum (ER) and the mitochondria, in the regulation of the [Ca 2+ ]i of mouse mesencephalic neurons were characterized. Both the K + -dependent Na + /Ca 2+ exchanger (NCKX) and the K + -independent Na + /Ca 2+ exchanger (NCX) can be detected and are functional in DA and non-DA neurons. NCX accounts for the larger component of Na + /Ca 2+ exchange activity. Single-cell RT-PCR analysis showed each individual neuron expressed a distinct set of the Na + /Ca 2+ exchangers. Furthermore, the Na + /Ca 2+ exchangers play prominent roles in removing [Ca 2+ ]i induced by glutamate but not [Ca 2+ ]i induced by depolarization. The mitochondria serve as a major Ca 2+ sink and are functionally located close to NCX. In contrast, the ER is functionally located close to NCKX and acts primarily as a Ca 2+ source with marginal effects. This study reveals that the Na + /Ca 2+ exchangers, the ER and the mitochondria, which cooperate interactively, act similarly when regulating [Ca 2+ ]i in mesencephalic DA and non-DA neurons. The heterogeneous expression of multiple types of Na + /Ca 2+ exchangers and the quantitative differences found in [Ca 2+ ]i regulation, together with other risk factors specific to DA neurons such as dopamine oxidation resulting in oxidative stress, may drive these cells to undergo selective degeneration.