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INSTITUTE OF PHYSIOLOGY CAS

Cutting-edge science for health

Laboratory of Cellular and Molecular Neuroendocrinology

Laboratory of Cellular and Molecular Neuroendocrinology

The 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

Sivčev; Sonja - Slavíková; Barbora - Rupert; Marian - Ivetic; Milorad - Nekardová; Michaela - Kudová; Eva - Zemková; Hana . Synthetic testosterone derivatives modulate rat P2X2 and P2X4 receptor channel gating . Journal of Neurochemistry. 2019; 150(1); 28-43 . IF = 4.066 [ASEP] [ doi ]
Ivetic; Milorad - Bhattacharya; Anirban - Zemková; Hana . P2X2 Receptor Expression and Function Is Upregulated in the Rat Supraoptic Nucleus Stimulated Through Refeeding After Fasting . Frontiers in Cellular Neuroscience. 2019; 13(Jun 26)); 284 . IF = 3.921 [ASEP] [ doi ]
Zemková, Hana - Stojilkovic, S. S. Neurotransmitter receptors as signaling platforms in anterior pituitary cells . Molecular and Cellular Endocrinology 2018, roč. 463, C, p. 49-64 . IF = 3.693 [ASEP] [ doi ]
Svobodová, Irena - Bhattacharya, Anirban - Ivetic, Milorad - Bendová, Z. - Zemková, Hana . Circadian ATP Release in Organotypic Cultures of the Rat Suprachiasmatic Nucleus Is Dependent on P2X7 and P2Y Receptors . Frontiers in Pharmacology 2018, roč. 9, Mar 6, článku 192 . IF = 3.845 [ASEP] [ doi ]
Stojilkovic, S. S. - Bjelobaba, I. - Zemková, Hana . Ion Channels of Pituitary Gonadotrophs and Their Roles in Signaling and Secretion . Frontiers in Endocrinology. 2017, roč. 8, Jun 9, článku 126 . IF = 3.519 [ASEP] [ doi ]

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People

RNDr. Hana Zemková, CSc.
Head of the Laboratory
Ing. Irena Svobodová, Ph.D. 
Deputy Head of the Laboratory
MUDr. Tomáš Radil, DrSc.​ 
Senior Researcher
Anirban Bhattacharya, Ph.D.
Postdoctoral Fellow
Mgr. Vendula Stillerová (Tvrdoňová), Ph. D.
Postdoctoral Fellow
Mgr. Vojtěch Vávra, Ph.D.
Postdoctoral Fellow (on postdocoral position abroad)
Mgr. Milorad Ivetic
PhD Student 
  Mgr. Marian Rupert
PhD Student 
Ing. Hana Janoušková
Technician
Irina Kalová
Technician