Laboratoř se věnuje výzkumu membránových receptorů a sekrece v neuroendokrinních buňkách. Hlavní zájem je soustředěn na vztah mezi elektrickými událostmi v plazmatické membráně a signalizačními drahami receptorů. Laboratoř zkoumá membránové receptory a iontové kanály na buněčné a molekulární úrovni, zabývá se mechanismy, jakými hormony a neurotransmitery využívají vápník a cyklické nukleotidy k vnitrobuněčné signalizaci, a charakterizuje kanály, které se podílí na elektrické aktivitě, vápníkové signalizaci a uvolňování neurotransmiterů a hormonů.
Hlavní oblasti výzkumu:
- Purinergní signalizace v neuronech suprachiasmatického a supraoptického jádra hypothalamu.
- Ligandem aktivované iontové kanály a elektrická excitabilita hypofyzárních buněk
- Vztah mezi strukturou a funkcí purinergních P2X receptorových kanálů
Aktuální projekty
Existují nejasnosti týkající se možných rozdílů v ATP modulaci synaptického přenosu a elektrické aktivity v neuronech tvořících oxytocin a vazopresin. Používáme metody buněčné elektrofyziologie a vápníkového imagingu ke studiu těchto vlastností u hypotalamických neuronů v mozkových řezech potkana.
Více
Purinergní P2X receptory (P2X1-7) patří do rodiny ligandem-aktivovaných iontových kanálů, jejichž vazebná místa pro alosterické modulátory nejsou stále plně objasněny. Aktivace těchto receptorů je nejdůležitější signalizační dráha extracelulárního adenosin 5'-trifosfátu (ATP) v neuroendokrinních buňkách.
Více
Úspěchy
The ATP-gated P2X7 receptor channel operates as a cytolytic and apoptotic receptor but also controls sustained cellular responses, including cell growth, proliferation and secretion. Experimental data suggest that that aromatic residues in the upper part of the first transmembrane domain are critical for both the P2X7R channel pore opening and receptor sensitization, and residues located at or below the intersection of the second transmembrane domains control its conductivity.
Více
Allosteric modulators of ligand-gated receptor channels induce conformational changes of the entire protein that alter potencies and efficacies for orthosteric ligands, expressed as the half maximal effective concentration and maximum current amplitude, respectively. The influence of allostery on channel pore size, an issue not previously addressed, was studied.
Více
Ivermectin is a large lipophilic molecule that acts as a positive allosteric regulator of several ligand-gated channels including the glutamate-gated chloride channel, gamma aminobutyric acid type-A receptor, glycine receptor, neuronal alpha7-nicotinic receptor and purinergic P2X4 receptor. This review summarizes what is currently known about ivermectin binding and modulation of Cys-loop receptor family of ligand-gated ion channels and what are the critical structural determinants underlying potentiation of the P2X4 receptor channel.
Více
Corticotorpin releasing hormone (CRH), a key regulator of HPA axis, is secreted by hypothalamic paraventricular neurons into the hypophysial portal system and stimulates ACTH secretion in pituitary corticotorphs. The data show that resting membrane potential in corticotrophs depends on background voltage-insensitive sodium conductance, and that CRH has biphasic actions: a depolarizing effect driven by a cationic conductance at basal concentrations in pituitary portal circulation and an inhibitory effect at higher stress CRH concentrations
Více
Publikace
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Circadian ATP Release in Organotypic Cultures of the Rat Suprachiasmatic Nucleus Is Dependent on P2X7 and P2Y Receptors
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Frontiers in Pharmacology 2018, roč. 9, Mar 6, článku 192
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Stojilkovic, S. S. - Bjelobaba, I. - Zemková, Hana
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Mackay, L. - Zemková, Hana - Stojilkovic, S. S. - Sherman, A. - Khadra, A.
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Fletcher, P. A. - Zemková, Hana - Stojilkovic, S. S. - Sherman, A.
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Zemková, Hana - Tomič, M. - Kučka, M. - Aguilera, G. - Stojilkovic, S. S.
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Zemková, Hana - Khadra, A. - Rokic, Milos Boro - Tvrdoňová, Vendula - Sherman, A. - Stojilkovic, S. S.
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Jindřichová, Marie - Bhattacharya, Anirban - Rupert, Marian - Skopek, Petr - Obšil, T. - Zemková, Hana
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Zemková, Hana - Tvrdoňová, Vendula - Bhattacharya, Anirban - Jindřichová, Marie
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Allosteric modulation of ligand gated ion channels by ivermectin
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Physiological Research 2014, roč. 63, suppl.1, s215-s224. ISSN 0862-8408.
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Tvrdoňová, Vendula - Rokic, Milos Boro - Stojilkovic, S. S. - Zemková, Hana
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Identification of Functionally Important Residues of the Rat P2X4 Receptor by Alanine Scanning Mutagenesis of the Dorsal Fin and Left Flipper Domains
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PLoS ONE 2014, roč. 9, 11, e112902. ISSN 1932-6203.
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Rokic, Milos Boro - Stojilkovic, S. S. - Zemková, Hana
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Structural and functional properties of the rat P2X4 purinoreceptor extracellular vestibule during gating
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Frontiers in Cellular Neuroscience 2014, roč. 8, jan 29, p. 3. ISSN 1662-5102.
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Bendová, Zdeňka - Janoušková, Hana - Svobodová, Irena
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Circadian rhythm and photic induction of the C-terminal splice variant of NMDAR1 subunit in the rat suprachiasmatic nucleus
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Synapse 2014, roč. 68, 2, p. 85-88. ISSN 0887-4476.
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Zemková, Hana - Kučka, M. - Bjelobaba, I. - Tomic, M. - Stojilkovic, S. S.
Multiple Cholinergic Signaling Pathways in Pituitary Gonadotrophs
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Endocrinology, 2013, Vol. 154, 1, p. 421-433
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Rokic, Milos Boro - Stojilkovic, S. S. - Vávra, Vojtěch - Kuzyk, Pavlo - Tvrdoňová, Vendula - Zemková, Hana
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Multiple Roles of the Extracellular Vestibule Amino Acid Residues in the Function of the Rat P2X4 Receptor
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PLoS ONE, 2013, Vol. 8, 3, e59411
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Khadra, A. - Tomic, M. - Yan, Z. - Zemková, Hana - Sherman, A. - Stojilkovic, S. S.
Dual Gating Mechanism and Function of P2X7 Receptor Channels
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Bhattacharya, Anirban - Vávra, Vojtěch - Svobodová, Irena - Bendová, Z. - Vereb, G. - Zemková, Hana
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Potentiation of Inhibitory Synaptic Transmission by Extracellular ATP in Rat Suprachiasmatic Nuclei
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Kučka, M. - Kretschmannová, K. - Stojilkovic, S. S. - Zemková, Hana - Tomic, M.
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Physiological Research, 2012, Vol. 61, 3, p. 267-275
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Jindřichová, Marie - Kuzyk, Pavlo - Li, S. - Stojilkovic, S. S. - Zemková, Hana
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Conserved ectodomain cysteines are essential for rat P2X7 receptor trafficking
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Jindřichová, Marie - Lansdell, S. J. - Millar, N. S.
Changes in Temperature Have Opposing Effects on Current Amplitude in alpha 7 and alpha 4 beta 2 Nicotinic Acetylcholine Receptors
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PLoS ONE, 2012, Vol. 7, 2, e32073
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Zemková, Hana - Stojilkovič, S.S. - Klein, D. C.
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Vávra, Vojtěch - Bhattacharya, Anirban - Zemková, Hana
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Petrenko, N. - Khafizov, K. - Tvrdoňová, Vendula - Skorinkin, A. - Giniatullin, R.
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Jindřichová, Marie - Khafizov, K. - Skorinkin, A. - Fayuk, D. - Bart, G. - Zemková, Hana - Giniatullin, R.
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Zemková, Hana - Kučka, M. - Li, S. - Gonzales-Iglesias, A. E. - Tomic, M. - Stojilkovic, S. S.
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Stojilkovic, S. S. - Yan, Z. - Obšil, T. - Zemková, Hana
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Structural Insights into the Function of P2X4: An ATP-Gated Cation Channel of Neuroendocrine Cells
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Stojilkovic, S. S. - He, M. L. - Koshimizu, T. - Balík, A. - Zemková, Hana
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Rokic, Milos Boro - Tvrdoňová, Vendula - Vávra, Vojtěch - Jindřichová, Marie - Obšil, T. - Stojilkovic, S. S. - Zemková, Hana
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Roles of conserved ectodomain cysteines of the rat P2X4 purinoreceptor in agonist binding and channel gating
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Kučka, M. - Kretschmannová, K. - Murano, T. - Wu, Ch. P. - Zemková, Hana - Ambudkar, S. V. - Stojilkovic, S. S.
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Molecular Pharmacology, 2010, Vol. 77, 2, p. 270-279
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Jindřichová, Marie - Vávra, Vojtěch - Obšil, Tomáš - Stojilkovic, S. S. - Zemková, Hana
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Journal of Neurochemistry, 2009, Vol. 109, 3, p. 923-934
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Balík, Aleš - Jindřichová, Marie - Bhattacharyya, Sharmistha - Zemková, Hana
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Zemková, Hana - Balík, Aleš - Jindřichová, Marie - Vávra, Vojtěch
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Zemková, H.W. - Bjelobaba, I. - Tomič, M. - Zemková, Hana - Stojilkovic, S. S.
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Mazna, Petr - Gryčová, Lenka - Balík, Aleš - Zemková, Hana - Friedlová, Eliška - Obšilová, Veronika - Obšil, Tomáš - Teisinger, Jan
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Jelínková, Irena - Vávra, Vojtěch - Jindřichová, Marie - Obšil, Tomáš - Zemková, H.W. - Zemková, Hana - Stojilkovic, S. S.
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Zemková, Hana - Yan, Z. - Liang, Z. - Jelínková, Irena - Tomič, M. - Stojilkovic, S. S.
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Buněčná lokalizace P2X2 receptorů v supraoptickém jádře hypotalamu. Imunohistochemie mozkového řezu potkana obsahujícího supraoptické jádro a optické chiasma (OC). P2X2R imunoreaktivita (zeleně) byla pozorována na tělech supraoptických neuronů. Barvení bylo provedeno pomocí protilátek proti P2X2R (zeleně) a označení neuronálních (červeně) a gliových (modrře) buněk. Měřítko je 50 µm.
