Current topics in membranes ; Vol. 49
648 s.
Advances in cardiology, ISSN 0065-2326 v. 42
viii, 298 s. : il. (některé barev.) ; 25 cm
- MeSH
- Cardiology MeSH
- Cardiovascular System MeSH
- Gap Junctions physiology drug effects MeSH
- Heart Diseases physiopathology MeSH
- Heart Conduction System * physiology MeSH
- Arrhythmias, Cardiac MeSH
- Publication type
- Monograph MeSH
- Conspectus
- Patologie. Klinická medicína
- NML Fields
- kardiologie
Throughout the brain, astrocytes form networks mediated by gap junction channels that promote the activity of neuronal ensembles. Although their inputs on neuronal information processing are well established, how molecular gap junction channels shape neuronal network patterns remains unclear. Here, using astroglial connexin-deficient mice, in which astrocytes are disconnected and neuronal bursting patterns are abnormal, we show that astrocyte networks strengthen bursting activity via dynamic regulation of extracellular potassium levels, independently of glutamate homeostasis or metabolic support. Using a facilitation-depression model, we identify neuronal afterhyperpolarization as the key parameter underlying bursting pattern regulation by extracellular potassium in mice with disconnected astrocytes. We confirm this prediction experimentally and reveal that astroglial network control of extracellular potassium sustains neuronal afterhyperpolarization via KCNQ voltage-gated K+ channels. Altogether, these data delineate how astroglial gap junctions mechanistically strengthen neuronal population bursts and point to approaches for controlling aberrant activity in neurological diseases.
- MeSH
- Action Potentials physiology MeSH
- Astrocytes * metabolism MeSH
- Potassium * metabolism MeSH
- KCNQ Potassium Channels * metabolism genetics MeSH
- Hippocampus * metabolism MeSH
- Connexins metabolism genetics MeSH
- Gap Junctions * metabolism MeSH
- Mice, Inbred C57BL MeSH
- Mice, Knockout MeSH
- Mice MeSH
- Nerve Net metabolism MeSH
- Neurons metabolism MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- MeSH
- Carcinogenesis genetics MeSH
- Stem Cells physiology pathology MeSH
- Colorectal Neoplasms * drug therapy surgery physiopathology pathology MeSH
- Connexins physiology drug effects MeSH
- Humans MeSH
- Cell Communication drug effects MeSH
- Intercellular Signaling Peptides and Proteins genetics MeSH
- Neoplastic Stem Cells drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Newspaper Article MeSH
Direct cell-to-cell communication in the heart is maintained via gap junction channels composed of proteins termed connexins. Connexin channels ensure molecular and electrical signals propagation and hence are crucial in myocardial synchronization and heart function. Disease-induced gap junctions remodeling and/or an impairment or even block of intercellular communication due to acute pathological conditions results in derangements of myocardial conduction and synchronization. This is critical in the development of both ventricular fibrillation, which is a major cause of sudden cardiac death and persistent atrial fibrillation, most common arrhythmia in clinical practice often resulting in stroke. Many studies suggest that alterations in topology (remodeling), expression, phosphorylation and particularly function of connexin channels due to age or disease are implicated in the development of these life-threatening arrhythmias. It seems therefore challenging to examine whether compounds that could prevent or attenuate gap junctions remodeling and connexin channels dysfunction can protect the heart against arrhythmias that cause sudden death in humans. This assumption is supported by very recent findings showing that an increase of gap junctional conductance by specific peptides can prevents atrial conduction slowing or re-entrant ventricular tachycardia in ischemic heart. Suppression of ischemia-induced dephosphorylation of connexin seems to be one of the mechanisms involved. Another approach for identifying novel treatments is based on the hypothesis that even non-antiarrhythmic drugs with antiarrhythmic ability can modulate gap junctional communication and hence attenuate arrhythmogenic substrates.
- MeSH
- Anti-Arrhythmia Agents therapeutic use MeSH
- Ventricular Fibrillation drug therapy metabolism MeSH
- Atrial Fibrillation drug therapy metabolism MeSH
- Phosphorylation MeSH
- Connexin 43 metabolism MeSH
- Humans MeSH
- Gap Junctions drug effects metabolism pathology MeSH
- Cell Communication drug effects MeSH
- Myocardium metabolism pathology MeSH
- Arrhythmias, Cardiac drug therapy metabolism pathology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Závěrečná zpráva o řešení grantu Interní grantové agentury MZ ČR
Přeruš. str. : il. ; 32 cm
Biologický mechanismus účinku modelového tumor promotoru Ethylenglykolu na mezibuněčné komunikace u savčích somatických buněk in vitro metodami metabolic cooperation assay a Scrape loading,za účelem interpretace procesu karcinogeneze.
- MeSH
- Ethylene Glycol MeSH
- Intercellular Junctions antagonists & inhibitors MeSH
- Neoplasms etiology MeSH
- Congenital Abnormalities etiology MeSH
- Conspectus
- Biologické vědy
- NML Fields
- biologie
- NML Publication type
- závěrečné zprávy o řešení grantu IGA MZ ČR
UNLABELLED: Dysregulation of gap junctional intercellular communication (GJIC) has been associated with different pathologies, including cancer; however, molecular mechanisms regulating GJIC are not fully understood. Mitogen Activated Protein Kinase (MAPK)-dependent mechanisms of GJIC-dysregulation have been well-established, however recent discoveries have implicated phosphatidylcholine-specific phospholipase C (PC-PLC) in the regulation of GJIC. What is not known is how prevalent these two signaling mechanisms are in toxicant/toxin-induced dysregulation of GJIC, and do toxicants/toxins work through either signaling mechanisms or both, or through alternative signaling mechanisms. Different chemical toxicants were used to assess whether they dysregulate GJIC via MEK or PC-PLC, or both Mek and PC-PLC, or through other signaling pathways, using a pluripotent rat liver epithelial oval-cell line, WB-F344. Epidermal growth factor, 12-O-tetradecanoylphorbol-13-acetate, thrombin receptor activating peptide-6 and lindane regulated GJIC through a MEK1/2-dependent mechanism that was independent of PC-PLC; whereas PAHs, DDT, PCB 153, dicumylperoxide and perfluorodecanoic acid inhibited GJIC through PC-PLC independent of Mek. Dysregulation of GJIC by perfluorooctanoic acid and R59022 required both MEK1/2 and PC-PLC; while benzoylperoxide, arachidonic acid, 18β-glycyrrhetinic acid, perfluorooctane sulfonic acid, 1-monolaurin, pentachlorophenol and alachlor required neither MEK1/2 nor PC-PLC. Resveratrol prevented dysregulation of GJIC by toxicants that acted either through MEK1/2 or PC-PLC. Except for alachlor, resveratrol did not prevent dysregulation of GJIC by toxicants that worked through PC-PLC-independent and MEK1/2-independent pathways, which indicated at least two other, yet unidentified, pathways that are involved in the regulation of GJIC. IN CONCLUSION: the dysregulation of GJIC is a contributing factor to the cancer process; however the underlying mechanisms by which gap junction channels are closed by toxicants vary. Thus, accurate assessments of risk posed by toxic agents, and the role of dietary phytochemicals play in preventing or reversing the effects of these agents must take into account the specific mechanisms involved in the cancer process.
- MeSH
- Principal Component Analysis MeSH
- Cell Line MeSH
- Butadienes pharmacology MeSH
- Phosphatidylcholines metabolism MeSH
- Type C Phospholipases metabolism MeSH
- Rats MeSH
- Gap Junctions drug effects metabolism MeSH
- Nitriles pharmacology MeSH
- Rats, Inbred F344 MeSH
- Bridged-Ring Compounds pharmacology MeSH
- Stilbenes pharmacology MeSH
- Thiones pharmacology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
