Background: Astrocytes were conceived for decades only as supporting cells of the brain. However, the observation of Ca2+ waves in astrocyte synctitia, their neurotransmitter receptor expression and gliotransmitter secretion suggested a role in information handling, conception that has some controversies. (SN-AmcIP3) is supported by different reports. However, some models contradict this idea and Ca2+ stores are 1000 ± 325 nm apart from the Postsynaptic Density in the Perisynaptic Astrocyte Projections (PAP's), suggesting that SN-AmcIP3 is extrasynaptic. However, this assumption does not consider IP3 Diffusion Coefficient (), that activates IP3 Receptor (IP3R) releasing Ca2+ from intracellular stores.
Results: In this work we idealized a model of a PAP (PAPm) to perform an order of magnitude analysis of IP3 diffusion using a transient mass diffusion model. This model shows that IP3 forms a concentration gradient along the PAPm that reaches the steady state in milliseconds, three orders of magnitude before IP3 degradation. The model predicts that IP3 concentration near the Ca2+ stores may activate IP3R, depending upon Phospholipase C (PLC) number and activity. Moreover, the PAPm supports that IP3 and extracellular Ca2+ entry synergize to promote global Ca2+ transients.
Conclusion: The model presented here indicates that Ca2+ stores position in PAP's does not limit SN-AmcIP3.
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http://dx.doi.org/10.1186/s13628-018-0043-3 | DOI Listing |
Pharmacol Res
January 2025
Gill Institute for Neuroscience; Dept. of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405. Electronic address:
Δ-tetrahydrocannabinol (THC), the chief psychoactive ingredient of cannabis, acts in the brain primarily via cannabinoid CB1 receptors. These receptors are implicated in several forms of synaptic plasticity - depolarization-induced suppression of excitation (DSE), metabotropic suppression of excitation (MSE), long term depression (LTD) and activation-dependent desensitization. Cultured autaptic hippocampal neurons express all of these, illustrating the rich functional and temporal heterogeneity of CB1 at a single set of synapses.
View Article and Find Full Text PDFPLoS Genet
January 2025
Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.
Inositol 1,4,5-trisphosphate receptors (IP3R) mediate Ca2+ release from intracellular stores, contributing to complex regulation of numerous physiological responses. The involvement of the three IP3R genes (ITPR1, ITPR2 and ITPR3) in inherited human diseases has started to shed light on the essential roles of each receptor in different human tissues and cell types. Variants in the ITPR3 gene, which encodes IP3R3, have recently been found to cause demyelinating sensorimotor Charcot-Marie-Tooth neuropathy type 1J (CMT1J).
View Article and Find Full Text PDFFoods
December 2024
Food Technology and Innovation Research Center of Excellence, School of Agricultural Technology and Food Industry, Walailak University, Nakhon Si Thammarat 80160, Thailand.
Genetic differences typically cause differences in the structure and function of proteins in meat. The objective of this research was to examine the biochemical characteristics and functional behavior of proteins in fresh composite meat from Thai Ligor hybrid chicken (LC) and commercial broiler chicken (BC). The composite meat samples, which comprise minced breast and thigh without skin from 20 chicken carcasses in a 1:1 (/) ratio, were randomly selected for analysis using the completely randomized design (CRD).
View Article and Find Full Text PDFFront Mol Biosci
December 2024
Swansea University Medical School, Institute of Life Science, Swansea, United Kingdom.
Aims: Mutations in the cardiac ryanodine receptor (RyR2) are associated with catecholaminergic polymorphic ventricular tachycardia (CPVT). This study investigates the underlying molecular mechanisms for CPVT mutations within the RyR2 N-terminus domain (NTD).
Methods And Results: We consulted the high-resolution RyR2 structure in both open and closed configuration to identify mutations G357S/R407I and A77T, which lie within the NTD intra- and inter-subunit interface with the Core Solenoid (CSol), respectively.
BMC Med
January 2025
Physiological Institute, University of Regensburg, University Street 31, 93053, Regensburg, Germany.
Background: Dystonia is a common neurological hyperkinetic movement disorder that can be caused by mutations in anoctamin 3 (ANO3, TMEM16C), a phospholipid scramblase and ion channel. We previously reported patients that were heterozygous for the ANO3 variants S651N, V561L, A599D and S651N, which cause dystonia by unknown mechanisms.
Methods: We applied electrophysiology, Ca measurements and cell biological methods to analyze the molecular mechanisms that lead to aberrant intracellular Ca signals and defective activation of K channels in patients heterozygous for the ANO3 variants.
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