Calcium Homeostasis in Glia and Neurons

Introduction to Calcium Homeostasis

The calcium concentration fluctuation in cells serves as the signal for various processes in neurons. And Ca²⁺ can trigger the release of neurotransmitters. What’s more, Ca²⁺ plays important roles in multiple neuronal functions, including synaptic plasticity, neuronal excitability, integration of electrical signals, gene expression, metabolism, and programmed cell death. Due to the key role in processes in neuronal excitability, calcium homeostasis is tightly regulated in glia and neurons. Recent studies have shown that impaired calcium homeostasis will lead to the occurrence of aging and the increased sensitivity of related neurons to injury.

Fig.1 This is a schematic representation of the main Ca2+ steady-state mechanical component in neurons.¹

Molecular Mechanisms for Neuronal Calcium Homeostasis

Recent studies showed that the passive influx of calcium ions is achieved through the plasma membrane Ca²⁺ channel along its electrochemical gradient. According to the control mechanism between the open and closed conformations, these channels can be classed into two major groups, which are voltage-gated Ca²⁺ channels and channels gated by ligand binding.

• Channels gated by voltage are multi-protein complexes composed of a series of subunits, such as α1, α2δ, β1-4, and γ. Among them, the α1 is the largest subunit associated with distinct auxiliary protein subunits. The pharmacological and physiological diversity of the Ca²⁺ channel is mainly derived from the existence of multiple α1 subunits, and these auxiliary subunits can regulate the functional properties of the Ca²⁺ channel complex.
• Channels gated by ligand binding refers to the channel activation caused by the interaction between the ligand and its plasma membrane receptor. L-glutamate has been served as the most prominent ligand of this type in the nervous system. In the vertebrate central nervous system (CNS), it is the most widespread excitatory transmitter that activates two classes of receptors, including ionotropic receptors and metabotropic receptors.

Intracellular Calcium Homeostasis in Neurons

In neurons, there are a series of channels, buffers, as well as sensors in the endoplasmic reticulum (ER) to act as a dynamic Ca²⁺ store. Under physiological stimulation, Ca²⁺ can be released by ER. In Golgi, the Ca²⁺ uptake involves two groups of Ca²⁺ pumps: Sarco(endo)plasmic reticulum Ca²⁺ ATPases (SERCAs) and secretory-pathway Ca²⁺-ATPases (SPCAs). Recent studies have shown that the contribution of SERCAs and SPCAs for Ca²⁺ uptake seems to be cell-type-dependent. In addition, mitochondria also function as Ca²⁺ buffers.

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Reference

1. Nikoletopoulou, V. Tavernarakis, N.; Calcium homeostasis in aging neurons. Frontiers in genetics. 2012, 3: 200. Distributed under Open Access license CC BY 4.0, without modification.