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Membrane properties of NG2 glia in CNS
Knotek, Tomáš ; Anděrová, Miroslava (advisor) ; Hrčka Krausová, Barbora (referee)
NG2 glia represent a new type of glial cells in central nervous system, which does not belong to astrocytes, oligodendrocyte or microglia. and their most frequent marker is chondroitine sulphate proteoglycan NG2. These cells keep their proliferation ability in adult brain and it is generally accepted that they can differentiate into oligodendrocytes. This thesis summarize the current knowledge about membrane properties of NG2 glia, namely expression of numerous types of ion channels and ionotropic and metabotropic receptor on their membrane. NG2 glia express outwardly and inwardly rectifying K+ channels, Ca2+ activated K+ channels and two-pore domain K+ channels. Interestingly, they also express voltage gated Na+ channels, L, T, P/Q and N type Ca2+ channels and voltage gated Cl- channels. Furthermore, nonspecific cationic channels, such as HCN and TRP, were identified in NG2 glia and they express Na+ /Ca2+ exchanger at high level. There are also ionotropic and metabotropic glutamate and GABA receptors on NG2 glia membrane, together with nicotinic and muscarinic receptors, adrenergic and glycine receptors, metabotropic and ionotropic purinergic receptors, receptors for serotonine, dopamine and histamine. Ion channels and receptors in NG2 glia play an important role in their proliferation,...
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Cannabinoid signalling and its physiological significance
Pavluch, Vojtěch ; Novotný, Jiří (advisor) ; Moravcová, Simona (referee)
Lidská společnost je ve styku s kanabinoidními látkami již od starověku. Ať už lidé využívali rostlinnou biomasu nebo bylinné léčitelství, bylo konopí vždy předmětem diskuzí. Poznatky objasňující molekulární principy účinku látek obsažených přírodně jen v konopí jsou však známy jen několik málo desítek let. Cílem této práce je charakterizovat subtypy receptorů, na které se kanabinoidy vážou, molekulární mechanismy jejich působení, následné konsekvence ve fyziologii a také poukázat na potenciální uplatnění jak rostlinných, tak syntetických kanabinoidů v lékařství. Kanabinoidní receptory jsou hojně se vyskytující podskupinou integrálních membránových receptorů, spadající do velké rodiny receptorů spřažených s G-proteiny. Vzhledem k ubikviternímu výskytu v organismu tyto receptory po aktivaci příslušnými lipofilními ligandy ovlivňují celou škálu fyziologických pochodů. Vazba kanabinoidních látek na daný subtyp těchto receptorů spouští specifickou signální kaskádu v buňce a ovlivňuje tak určitým způsobem buněčný metabolismus. Studium kanabinoidních receptorů a jejich ligandů přispívá k porozumění procesům zahrnujícím tvorbu paměti a učení, ale také mechanismům zapojeným v analgézii, imunomodulaci a buněčné proliferaci. Tyto receptory však ovlivňují také fyziologii kardiovaskulárního systému nebo...
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Spontaneous calcium permeability of ionic channel of P2X receptor after substitution ofconserved tyrosine in the 1st transmembrae domajn
Rupert, Marian ; Zemková, Hana (advisor) ; Balík, Aleš (referee)
Purinergic receptors are membrane ion channels that are activated by extracellular ATP. In vertebrates, seven genes encode subunits of P2X receptors. The subunits, designated P2X1-7, are 40 - 50% identical in amino acid sequences. P2X receptors are composed of three subunits and are found as homo- and heterotrimers in tissues of vertebrates. P2X receptors have a wide distribution in the organism, functional receptors are found in neurons, glial cells, muscle cells and also in nonexcitable tissues as epithelial, endothelial, and in hemopoietic tissue. Purinergic signalling plays an important role in pain transmission, at CNS injury and immune processes. P2X receptor subunit consists of two transmembrane domains, extracellular domain and intracellular N-and C-termini. Each transmembrane domain contains two amino acids conserved across all P2X subunits. In the first transmembrane domain receptor P2X2 are that Gly30 and Tyr43. In previous experiments performed on P2X2 receptor, electrophysiological measurements demonstrated that substitution of conserved Tyr43 in the first transmembrane domain with alanine prolongs the deactivation time of ion channel after agonist wash out. This work is focused on clarifying the role of conserved tyrosine in the process of opening and closing of ion channel of P2X...
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Structure, function and pharmacology of NMDA receptors
Švehla, Pavel ; Vyklický, Ladislav (advisor) ; Bendová, Zdeňka (referee)
Glutamate is a major excitatory neurotransmitter between neurons in the central nervous system. The effect of glutamate is caused by the activation of distinct ionotropic glutamate channels: AMPA, kainate and NMDA receptors. NMDA receptors play a critical role in the synaptic plasticity and excitotoxicity. Despite the crucial role of these receptors in the right function of the brain, their overexcitation under pathological conditions may result in such neurological disorders as Alzheimers, Parkinsons and Huntingtons diseases. The aim of this work is to review available data concerning the molecular structure of NMDA subtype of ionotropic glutamate receptors, their pharmacology and therapeutic potential.
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Neurosteroid modulation of ligand-gated ion-channel activity
Krausová, Barbora ; Vyklický, Ladislav (advisor) ; Moravec, Jan (referee)
The term neurosteroids refers to steroids that are synthetized in the nervous tissue from cholesterol or steroidal precursors from peripheral sources. These compounds affect the neuronal excitability by modulating the function of some ligand-gated ion channels. NMDA (N methyl D aspartate) receptors are glutamate gated ion channels involved in excitatory synaptic transmission, synaptic plasticity and excitotoxicity. GABAA ( aminobutyric acid type A) receptors mediate most of the inhibitory synaptic transmission in the mammalian brain and are targeted by many clinically important drugs. Function of NMDA and GABAA receptors can by affected by neurosteroids, both positively and negatively. The aim of this work is to summarize the current knowledge about the neurosteroid effects on the function of GABAA a NMDA receptors and suggest the physiological role and the potential therapeutic use of the neurosteroids as a regulator of some functions of the central nervous system.
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