• MeSH
• kardiologie MeSH
• kardiovaskulární systém MeSH
• mezerový spoj fyziologie   účinky léků   MeSH
• nemoci srdce patofyziologie   MeSH
• převodní systém srdeční * fyziologie   MeSH
• srdeční arytmie MeSH
• Publikační typ
• monografie MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• kardiologie

• MeSH
• chemoprofylaxe metody   MeSH
• konexiny MeSH
• mezibuněčná komunikace MeSH
• mezibuněčné spoje MeSH
• nádory farmakoterapie   prevence a kontrola   MeSH

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
• akční potenciály fyziologie   MeSH
• astrocyty * metabolismus   MeSH
• draslík * metabolismus   MeSH
• draslíkové kanály KCNQ * metabolismus   genetika   MeSH
• hipokampus * metabolismus   MeSH
• konexiny metabolismus   genetika   MeSH
• mezerový spoj * metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• nervová síť metabolismus   MeSH
• neurony metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• karcinogeneze genetika   MeSH
• kmenové buňky fyziologie   patologie   MeSH
• kolorektální nádory * farmakoterapie   chirurgie   patofyziologie   patologie   MeSH
• konexiny fyziologie   účinky léků   MeSH
• lidé MeSH
• mezibuněčná komunikace účinky léků   MeSH
• mezibuněčné signální peptidy a proteiny genetika   MeSH
• nádorové kmenové buňky účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• novinové články MeSH

• Konspekt
• Buněčná biologie. Cytologie
• NLK Obory
• biologie
• cytologie, klinická cytologie

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
• antiarytmika terapeutické užití   MeSH
• fibrilace komor farmakoterapie   metabolismus   MeSH
• fibrilace síní farmakoterapie   metabolismus   MeSH
• fosforylace MeSH
• konexin 43 metabolismus   MeSH
• lidé MeSH
• mezerový spoj účinky léků   metabolismus   patologie   MeSH
• mezibuněčná komunikace účinky léků   MeSH
• myokard metabolismus   patologie   MeSH
• srdeční arytmie farmakoterapie   metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

• MeSH
• excitační postsynaptické potenciály genetika   MeSH
• finanční podpora výzkumu jako téma MeSH
• lidé MeSH
• membránové potenciály fyziologie   MeSH
• mezerový spoj fyziologie   metabolismus   MeSH
• synaptické membrány chemie   metabolismus   mikrobiologie   sekrece   MeSH
• Check Tag
• lidé MeSH

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
• ethylenglykol MeSH
• mezibuněčné spoje antagonisté a inhibitory   MeSH
• nádory etiologie   MeSH
• vrozené vady etiologie   MeSH

• Konspekt
• Biologické vědy
• NLK Obory
• biologie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR

• MeSH
• ethylenglykol farmakologie   MeSH
• finanční podpora výzkumu jako téma MeSH
• konexiny biosyntéza   metabolismus   MeSH
• křečci praví MeSH
• mezerový spoj účinky léků   MeSH
• zvířata MeSH
• Check Tag
• křečci praví MeSH
• zvířata MeSH

We hypothesized that hypertension-related myocardial remodeling characterized by hypertrophy and fibrosis might be accompanied by cell-to-cell gap junction alterations that may account for increased arrhythmogenesis. Intercellular junctions and expression of gap junction protein connexin-43 were analyzed in rat heart tissues from both spontaneous (SHR) and L-NAME model of hypertension. Isolated heart preparation was used to examine susceptibility of the heart to lethal ventricular fibrillation induced by low potassium perfusion. Ultrastructure observation revealed enhanced neoformation of side-to-side type while internalization of end-to-end type (intercalated disc-related) of gap junctions prevailed in the myocardium of rats suffering from either spontaneous or L-NAME-induced hypertension. In parallel, immunolabeling showed increased number of connexin-43 positive gap junctions in lateral cell membrane surfaces, particularly in SHR. Besides, focal loss of immunopositive signal was observed more frequently in hearts of rats treated with L-NAME. There was a significantly higher incidence of hypokalemia-induced ventricular fibrillation in hypertensive compared to normotensive rat hearts. We conclude that adaptation of the heart to hypertension-induced mechanical overload results in maladaptive gap junction remodeling that consequently promotes development of fatal arrhythmias.

• MeSH
• draslík MeSH
• fibrilace komor chemicky indukované   metabolismus   MeSH
• fyziologická adaptace MeSH
• hypertenze metabolismus   patologie   MeSH
• hypokalemie metabolismus   MeSH
• konexin 43 metabolismus   MeSH
• krysa rodu rattus MeSH
• mezerový spoj metabolismus   MeSH
• myokard metabolismus   ultrastruktura   MeSH
• potkani inbrední SHR MeSH
• potkani Wistar MeSH
• srdeční komory mikrobiologie   virologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH