Dataset Information

GABA_A and GABA_B Receptors Mediate GABA-Induced Intracellular Ca²⁺ Signals in Human Brain Microvascular Endothelial Cells.

ABSTRACT: Numerous studies recently showed that the inhibitory neurotransmitter, γ-aminobutyric acid (GABA), can stimulate cerebral angiogenesis and promote neurovascular coupling by activating the ionotropic GABA_A receptors on cerebrovascular endothelial cells, whereas the endothelial role of the metabotropic GABA_B receptors is still unknown. Preliminary evidence showed that GABA_A receptor stimulation can induce an increase in endothelial Ca²⁺ levels, but the underlying signaling pathway remains to be fully unraveled. In the present investigation, we found that GABA evoked a biphasic elevation in [Ca²⁺]_i that was initiated by inositol-1,4,5-trisphosphate- and nicotinic acid adenine dinucleotide phosphate-dependent Ca²⁺ release from neutral and acidic Ca²⁺ stores, respectively, and sustained by store-operated Ca²⁺ entry. GABA_A and GABA_B receptors were both required to trigger the endothelial Ca²⁺ response. Unexpectedly, we found that the GABA_A receptors signal in a flux-independent manner via the metabotropic GABA_B receptors. Likewise, the full Ca²⁺ response to GABA_B receptors requires functional GABA_A receptors. This study, therefore, sheds novel light on the molecular mechanisms by which GABA controls endothelial signaling at the neurovascular unit.

SUBMITTER: Negri S

PROVIDER: S-EPMC9739010 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

GABAA and GABAB Receptors Mediate GABA-Induced Intracellular Ca2+ Signals in Human Brain Microvascular Endothelial Cells.

Negri Sharon S Scolari Francesca F Vismara Mauro M Brunetti Valentina V Faris Pawan P Terribile Giulia G Sancini Giulio G Berra-Romani Roberto R Moccia Francesco F

Cells 20221130 23

Numerous studies recently showed that the inhibitory neurotransmitter, γ-aminobutyric acid (GABA), can stimulate cerebral angiogenesis and promote neurovascular coupling by activating the ionotropic GABAA receptors on cerebrovascular endothelial cells, whereas the endothelial role of the metabotropic GABAB receptors is still unknown. Preliminary evidence showed that GABAA receptor stimulation can induce an increase in endothelial Ca2+ levels, but the u ...[more]

PMID: 36497118

Similar Datasets

Project description:Pancreatic β-cells release insulin upon a rise in blood glucose. The precise mechanisms of stimulus-secretion coupling, and its failure in Diabetes Mellitus Type 2, remain to be elucidated. The consensus model, as well as a class of currently prescribed anti-diabetic drugs, are based around the observation that glucose-evoked ATP production in β-cells leads to closure of cell membrane ATP-gated potassium (KATP) channels, plasma membrane depolarisation, Ca2+ influx, and finally the exocytosis of insulin granules. However, it has been demonstrated by the inactivation of this pathway using genetic and pharmacological means that closure of the KATP channel alone may not be sufficient to explain all β-cell responses to glucose elevation. We have previously proposed that NAADP-evoked Ca2+ release is an important step in stimulus-secretion coupling in pancreatic β-cells. Here we show using total internal reflection fluorescence (TIRF) microscopy that glucose as well as the Ca2+ mobilising messenger nicotinic acid adenine dinucleotide phosphate (NAADP), known to operate in β-cells, lead to highly localised elementary intracellular Ca2+ signals. These were found to be obscured by measurements of global Ca2+ signals and the action of powerful SERCA-based sequestration mechanisms at the endoplasmic reticulum (ER). Building on our previous work demonstrating that NAADP-evoked Ca2+ release is an important step in stimulus-secretion coupling in pancreatic β-cells, we provide here the first demonstration of elementary Ca2+ signals in response to NAADP, whose occurrence was previously suspected. Optical quantal analysis of these events reveals a unitary event amplitude equivalent to that of known elementary Ca2+ signalling events, inositol trisphosphate (IP3) receptor mediated blips, and ryanodine receptor mediated quarks. We propose that a mechanism based on these highly localised intracellular Ca2+ signalling events mediated by NAADP may initially operate in β-cells when they respond to elevations in blood glucose.

Dataset Information

GABA_A and GABA_B Receptors Mediate GABA-Induced Intracellular Ca²⁺ Signals in Human Brain Microvascular Endothelial Cells.

Publications

GABA<sub>A</sub> and GABA<sub>B</sub> Receptors Mediate GABA-Induced Intracellular Ca<sup>2+</sup> Signals in Human Brain Microvascular Endothelial Cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets