Ionotropic glutamate receptors of the kainate and AMPA subtypes share a number of structural features, both topographical and in terms of stoichiometry. In addition, AMPA and kainate receptors share similar pharmacological and biophysical properties in that they are activated by common agonists and display rapid activation and desensitization characteristics. However, we show here that in contrast to AMPA receptor-mediated responses (native or recombinant GluR3 receptor), the response of native and recombinant (GluR6) kainate receptors to glutamate was drastically reduced in the absence of extracellular Na+ (i.e., when replaced by Cs+). Removal of Na+ increases the rate of desensitization, indicating that external Na+ modulates channel gating. Whereas the size of the substituting cation is important in mimicking the action of Na+ (Li+>K+>Cs+), modulation was voltage independent. These results indicate the existence of different gating mechanisms for AMPA and kainate receptors. By using chimeric AMPA-kainate receptors derived from GluR3 and GluR6, we have identified a key residue in the S2 segment of GluR6 (M770) that is largely responsible for the sensitivity of the receptor to external Na+. Thus, these results show the existence of a specific kainate receptor gating mechanism that requires external Na+ to be operative.
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http://dx.doi.org/10.1523/JNEUROSCI.23-25-08641.2003 | DOI Listing |
Curr Neuropharmacol
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Department of Pharmacy, DIFAR, Pharmacology and Toxicology Section, University of Genoa, Viale Cembrano 4, 16148, Genoa, Italy.
The central nervous system (CNS) is not an immune-privileged compartment, but it is intimately intertwined with the immune system. Among the components shared by the two compartments is the complement, a main constituent of innate immunity, which is also produced centrally and controls the development and organization of synaptic connections. Complement is considered a doubled-faced system that, besides controlling the physiological development of the central network, also subserves synaptic engulfment pivotal to the progression of neurodegenerative diseases.
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Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab, India.
Neuropathic pain, a challenging condition often associated with diabetes, trauma, or chemotherapy, impairs patients' quality of life. Current treatments often provide inconsistent relief and notable adverse effects, highlighting the urgent need for safer and more effective alternatives. This review investigates marine-derived bioactive compounds as potential novel therapies for neuropathic pain management.
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Department of Experimental Physiology and Pathophysiology, Medical University of Białystok, Ul. Mickiewicza 2A, 15-222, Białystok, Poland.
Although angiotensin 1-7 (Ang 1-7) and its role as a part of the "protective" axis of the renin-angiotensin system are well described in the literature, the mechanisms of its angiotensin II-like pressor and tachycardic effects following its acute central administration are not fully understood. It was the aim of the present study to examine which receptors contribute to the aforementioned cardiovascular effects. Ang 1-7 and antagonists for glutamate, GABA, vasopressin, thromboxane A (TP), α-adrenergic, and P2X purinoceptors or modulators of oxidative stress were injected into the paraventricular nucleus of the hypothalamus (PVN) of urethane-anesthetized male Wistar rats.
View Article and Find Full Text PDFProg Neurobiol
December 2024
Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich 52425, Germany; C. & O. Vogt Institute for Brain Research, Heinrich-Heine-University, Dusseldorf 40225, Germany.
Neurotransmitter receptors are key molecules in signal transmission in the adult brain, and their precise spatial and temporal balance expressions also play a critical role in normal brain development. However, the specific balance expression of multiple receptors during hippocampal development is not well characterized. In this study, we used quantitative in vivo receptor autoradiography to measure the distributions and densities of 18 neurotransmitter receptor types in the mouse hippocampal complex at postnatal day 7, and compared them with the expressions of their corresponding encoding genes.
View Article and Find Full Text PDFEnviron Microbiol
December 2024
School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand.
Oxylipin signalling is central in biology, mediating processes such as cellular homeostasis, inflammation and molecular signalling. It may also facilitate inter-partner communication in the cnidarian-dinoflagellate symbiosis, though this aspect remains understudied. In this study, four oxylipin receptors were characterised using immunohistochemistry and immunoblotting in the sea anemone Exaiptasia diaphana ('Aiptasia'): Prostaglandin E2 receptor 2 (EP2) and 4 (EP4), Transient Receptor Potential cation channel A1 (TRPA1) and Glutamate Receptor Ionotropic, Kainate 2 (GRIK2).
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