Extracellular Ca ²⁺ Acts as a Mediator of Communication from Neurons to Glia

Abstract

Defining the pathways through which neurons and astrocytes communicate may contribute to the elucidation of higher central nervous system functions. We investigated the possibility that decreases in extracellular calcium ion concentration ([Ca2+]e) that occur during synaptic transmission might mediate signaling from neurons to glia. Using noninvasive photolysis of the photolabile Ca2+ buffer diazo-2 {N-[2-[2-[2-[bis(carboxymethyl)amino]-5-(diazoacetyl)phenoxy]ethoxy]-4-methylphenyl]-N-(carboxymethyl)-, tetrapotassium salt} to reduce [Ca2+]e or caged glutamate to simulate glutamatergic transmission, we found that a local decline in extracellular Ca2+ triggered astrocytic adenosine triphosphate (ATP) release and astrocytic Ca2+ signaling. In turn, activation of purinergic P2Y1 receptors on a subset of inhibitory interneurons initiated the generation of action potentials by these interneurons, thereby enhancing synaptic inhibition. Thus, astrocytic ATP release evoked by an activity-associated decrease in [Ca2+]e may provide a negative feedback mechanism that potentiates inhibitory transmission in response to local hyperexcitability.

Astroglial connexin 43 sustains glutamatergic synaptic efficacy

“…Glutamine diffusion through the astroglial GJ network is of particular interest, because it may be involved in the neuroglial glutamine-glutamate cycle [32], necessary to fuel glutamate presynaptic pools and thereby supports excitatory synaptic transmission ( [33,34], but see [35]). Alternatively, Cx43 hemichannels could mediate release of energy metabolites or gliotransmitters sustaining excitatory synaptic transmission, because they have recently been shown to be involved in neuronal network activity [36] or memory consolidation [37]. Finally, Cx43 non-channel functions related to protein interactions, cell adhesion or intracellular signalling may also be involved in the regulation of synaptic transmission.…”

Intake of dairy products and calcium and prevalence of depressive symptoms during pregnancy in Japan: a cross‐sectional study

“…Higher calcium intake might be expected to moderate extracellular calcium fluctuations and prevent inhibitory transmission, resulting in a lower prevalence of depressive symptoms. 24 …”

Connexin and pannexin signaling pathways, an architectural blueprint for CNS physiology and pathology?

“…e in the range of 0.4-0.6 mM, comparable to what has been observed during epileptic activity, was required to trigger HC-mediated ATP release and astroglial [Ca 2? ] i increases [271]. In contrast, using Cx mimetic peptides, Chever and group recently provided evidence that astroglial Cx43 HCs are open under basal conditions in hippocampal slices and modulate moment-to-moment excitatory synaptic transmission in CA1 pyramidal neurons through ATP release.…”

“…Extracellular ATP and glutamate accumulation can promote neuronal and oligodendroglial death [286,333], while adenosine can affect neuronal function [271,338]. Both Panx1 channels and HCs form large pores of which excessive opening in cells exposed to stressful conditions is considered to be deleterious due to the loss of cytoplasmic integrity as well as the release of these neurotoxic substances [339,340].…”