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Cellular and Molecular Neuroendocrinology

Cellular and Molecular Neuroendocrinology

Laboratory is focused on the research of  membrane receptors and secretion in neuroendocrine cells, with a special emphasis on the interactions between plasma membrane electrical events and receptor-controlled pathways. The Laboratory investigates signaling pathways at the cellular and molecular levels, determines the manner in which hormones and neurotransmitters utilize calcium and cyclic nucleotides as intracellular messengers, and characterizes channels involved in electrical activity, calcium signaling, and release of hormones and neurotransmitters.

 

Main topics:

  • Purinergic signaling in neurons of suprachiasmatic and supraoptic nuclei of hypothalamus.
  • Ligand-gated ion channels and electrical excitability of pituitary cells
  • Relationship between structure and function of purinergic P2X receptor-channels

Projects

Achievements

Our new paper: Role of transmembrane domains in P2X7 receptor activation and sensitization

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. More

Our new paper: Allosteric modulation of P2X4 receptor channel conductivity.

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. More

Our new paper: Ivermectin action on ligand-gated ion channels

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. More

Our new paper: CRH-induced excitability in pituitary corticotrophs

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 More

Publications

Zemková, Hana - Tomič, M. - Kučka, M. - Aguilera, G. - Stojilkovic, S. S. Spontaneous and CRH-Induced Excitability and Calcium Signaling in Mice Corticotrophs Involves Sodium, Calcium, and Cation-Conducting Channels . Endocrinology. 2016, roč. 157, 4, p. 1576-1589 . IF = 4.286 [ASEP] [ doi ]
Zemková, Hana - Khadra, A. - Rokic, Milos Boro - Tvrdoňová, Vendula - Sherman, A. - Stojilkovic, S. S. Allosteric regulation of the P2X4 receptor channel pore dilation . Pflugers Archiv - European Journal of Physiology. 2015, Vol. 467, 4, p. 713-726 . IF = 3.654 [ASEP] [ doi ]
Jindřichová, Marie - Bhattacharya, Anirban - Rupert, Marian - Skopek, Petr - Obšil, T. - Zemková, Hana . Functional characterization of mutants in the transmembrane domains of the rat P2X7 receptor that regulate pore conductivity and agonist sensitivity . Journal of Neurochemistry. 2015, Vol. 133, 6, p. 815-827 . IF = 3.842 [ASEP] [ doi ]
Zemková, Hana - Tvrdoňová, Vendula - Bhattacharya, Anirban - Jindřichová, Marie . Allosteric modulation of ligand gated ion channels by ivermectin . Physiological Research 2014, roč. 63, suppl.1, s215-s224. ISSN 0862-8408. IF = 1.293 [ASEP]
Tvrdoňová, Vendula - Rokic, Milos Boro - Stojilkovic, S. S. - Zemková, Hana . Identification of Functionally Important Residues of the Rat P2X4 Receptor by Alanine Scanning Mutagenesis of the Dorsal Fin and Left Flipper Domains . PLoS ONE 2014, roč. 9, 11, e112902. ISSN 1932-6203. IF = 3.234 [ASEP] [ doi ]

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Contacts

Institute of Physiology AS CR, v.v.i.
Department of Cellular and Molecular Neuroendocrinology

Vídeňská 1083
14220 Prague 4
tel. +420 241 062 574
fax. +420 241 062 488
 

hana.zemkova@fgu.cas.cz

People

RNDr. Hana Zemková, CSc.
head of the department
Ing. Irena Svobodová, Ph.D. 
deputy head of department
MUDr. Tomáš Radil, DrSc.​ 
senior researcher
Anirban Bhattacharya, Ph.D.
postdoc 
Mgr. Vendula Stillerová (Tvrdoňová), Ph. D.
postdoc
Mgr. Vojtěch Vávra, Ph.D.
postdoc (on postdocoral position abroad)
Mgr. Milorad Ivetic
PhD student 
  Mgr. Marian Rupert
PhD student 
Ing. Hana Janoušková
lab technician
Irina Kalová
lab technician

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