Neuronal calcium signaling: function and dysfunction

Abstract

Calcium (Ca(2+)) is an universal second messenger that regulates the most important activities of all eukaryotic cells. It is of critical importance to neurons as it participates in the transmission of the depolarizing signal and contributes to synaptic activity. Neurons have thus developed extensive and intricate Ca(2+) signaling pathways to couple the Ca(2+) signal to their biochemical machinery. Ca(2+) influx into neurons occurs through plasma membrane receptors and voltage-dependent ion channels. The release of Ca(2+) from the intracellular stores, such as the endoplasmic reticulum, by intracellular channels also contributes to the elevation of cytosolic Ca(2+). Inside the cell, Ca(2+) is controlled by the buffering action of cytosolic Ca(2+)-binding proteins and by its uptake and release by mitochondria. The uptake of Ca(2+) in the mitochondrial matrix stimulates the citric acid cycle, thus enhancing ATP production and the removal of Ca(2+) from the cytosol by the ATP-driven pumps in the endoplasmic reticulum and the plasma membrane. A Na(+)/Ca(2+) exchanger in the plasma membrane also participates in the control of neuronal Ca(2+). The impaired ability of neurons to maintain an adequate energy level may impact Ca(2+) signaling: this occurs during aging and in neurodegenerative disease processes. The focus of this review is on neuronal Ca(2+) signaling and its involvement in synaptic signaling processes, neuronal energy metabolism, and neurotransmission. The contribution of altered Ca(2+) signaling in the most important neurological disorders will then be considered.

Progressive Degeneration of Dopaminergic Neurons through TRP Channel-Induced Cell Death

“…The ot337 allele was mapped on the right arm of CHRI (ϩ14 to ϩ26 cM) using highthroughput SNP mapping (Davis et al, 2005). Both ot337 and ot477 alleles were whole-genome sequenced using an Illumina platform followed by data analysis as previously described (Bigelow et al, 2009).…”

“…Ectopic expression of trp-4(d): trp-4(d) cDNA followed by unc-54 3ЈUTR was cloned under the osm-6 promoter (Collet et al, 1998) and injected into oyIs59 worms expressing osm-6::GFP at 30 ng/l, along with 60 ng/l rol-6 and 50 ng/l ttx-3::mcherry. Worms containing the ttx-3::mcherry coinjection marker were scored for degeneration of ADE, PHA, PHB, and PQR neurons.…”

“…Specifically, Ca 2ϩ dysregulation has been suggested to contribute to the etiology as well as progression of various neurological diseases (Bezprozvanny, 2009;Nikoletopoulou and Tavernarakis, 2012), including Parkinson's disease (Chan et al, 2007;Gandhi et al, 2009;), Alzheimer's disease (Bojarski et al, 2008), amyotrophic lateral sclerosis (Grosskreutz et al, 2010), and Huntington's disease (Giacomello et al, 2011;. Particularly relevant to intracellular Ca 2ϩ homeostasis is the family of Transient Receptor Potential (TRP) channels, known to be involved in initiating Ca 2ϩ entry pathways as well as maintaining cytosolic, endoplasmic reticulum (ER), and mitochondrial Ca 2ϩ levels (Gees et al, 2010).…”

A Novel Mutation in Isoform 3 of the Plasma Membrane Ca2+ Pump Impairs Cellular Ca2+ Homeostasis in a Patient with Cerebellar Ataxia and Laminin Subunit 1α Mutations

“…Since neurons are particularly dependent on the perfect regulation of their own Ca 2ϩ (3), a number of neuronal diseases reflect the incorrect functioning of the Ca 2ϩ controlling systems. Among these disease states, those linked to defects of the plasma membrane Ca 2ϩ ATPase (PMCA) 6 pumps are becoming increasingly important.…”

Nutritional strategies in the management of Alzheimer\'s disease: systematic review and meta-analysis

“…The aging process yields to a slight Ca 2+ dyshomeostasis resulting from the oxidative stress and the accumulation of energy metabolism remnants. Dysfunction of these Ca 2+ signaling pathways in the brain is implicated in neurodegenerative disease, among these AD, PD, cerebellar ataxia, amyotrophic lateral sclerosis (ALS), Huntington's disease (HD) and familial hemiplegic migraine (FHM) (102,103). It has been hypothesized that the aggregation of Aβ in AD induces a progressive increase in the resting level of Ca 2+ causing a deregulation of Ca 2+ signaling via direct effects on neurons and indirectly by inflammatory responses in microglia and astrocytes, which possibly influence cognition by interfering with the rhythm rheostat that controls the sleep/wake cycle.…”