Molecular theory of solvation for supramolecules and soft matter structures: application to ligand binding, ion channels, and oligomeric polyelectrolyte gelators

Soft Matter ◽  
2012 ◽  
Vol 8 (5) ◽  
pp. 1508-1520 ◽  
Author(s):  
Andriy Kovalenko ◽  
Alexander E. Kobryn ◽  
Sergey Gusarov ◽  
Olga Lyubimova ◽  
Xiangjun Liu ◽  
...  
Keyword(s):  
Ion Channels ◽  
Ligand Binding ◽  
Soft Matter ◽  
Molecular Theory

Ketamine inhibition of ligand binding to cholinergic receptors and ion channels

1982 ◽  
Vol 78 (3) ◽  
pp. 367-370 ◽  
Author(s):  
Robert S. Aronstam ◽  
Latha Narayanan ◽  
Deborah A. Wenger
Keyword(s):  
Ion Channels ◽  
Ligand Binding ◽  
Cholinergic Receptors

scholarly journals Quantifying the cooperative subunit action in a multimeric membrane receptor

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Nisa Wongsamitkul ◽  
Vasilica Nache ◽  
Thomas Eick ◽  
Sabine Hummert ◽  
Eckhard Schulz ◽  
...  
Keyword(s):  
Ion Channels ◽  
Ligand Binding ◽  
Cyclic Nucleotide ◽  
Binding Sites ◽  
Membrane Receptor ◽  
Membrane Receptors ◽  
Cooperative Action ◽  
The Individual ◽  
Insight Into

Abstract In multimeric membrane receptors the cooperative action of the subunits prevents exact knowledge about the operation and the interaction of the individual subunits. We propose a method that permits quantification of ligand binding to and activation effects of the individual binding sites in a multimeric membrane receptor. The power of this method is demonstrated by gaining detailed insight into the subunit action in olfactory cyclic nucleotide-gated CNGA2 ion channels.

scholarly journals Modulation of Calcium Signaling by Chemogenetic Tools to Elucidate the Pathogenesis of Primary Aldosteronism

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A294-A295
Author(s):  
Teresa Cosentino ◽  
Bakhta Fedlaoui ◽  
Isabelle Giscos-Douriez ◽  
Fabio Luiz Fernandes-Rosa ◽  
Christopher Magnus ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Ion Channels ◽  
Ligand Binding ◽  
Calcium Signaling ◽  
Intracellular Calcium ◽  
Acetylcholine Receptor ◽  
Cell Lines ◽  
Primary Aldosteronism ◽  
Calcium Entry ◽  
Steroidogenic Genes

Abstract Primary aldosteronism (PA) is the most frequent form of secondary arterial hypertension. The identification of germline or somatic mutations in different genes coding for ion channels (KCNJ5, CACNA1D, CACNA1H and CLCN2) and ATPases (ATP1A1 and ATP2B3) defines PA as a channelopathy. These mutations promote increased intracellular calcium concentrations and activation of calcium signaling, the main trigger for aldosterone biosynthesis. The aim of our study was to elucidate the mechanisms underlying the development of PA by modulating calcium signaling using chemogenetic tools. We have generated two different adrenocortical H295R_S2 cell lines stably expressing different chimeric ion channels generated by fusing the mutated extracellular ligand binding domain of the α7 nicotinic acetylcholine receptor to the ion pore domain of large Cys-loop receptor ion channel family; these receptors constitute PSAM (Pharmacologically Selective Actuator Modules). The mutations introduced in the ligand-binding domain allow to use synthetic ligands, PSEM (Pharmacologically Selective Effector Molecules) to activate the PSAM. We used two different PSAM: the chimeric receptor α7-5HT3 or a mutated acetylcholine receptor nAchR, allowing respectively modulation of sodium or calcium entry into the cells in response to the specific PSEM: Varenicline for α7-5HT3 or Compound 9S for mutated nAChR. The cells lines were characterized in terms of intracellular calcium concentrations, cell proliferation, aldosterone production and steroidogenic gene expression. Cells expressing α7-5HT3 treated for 24h with increasing concentrations of Varenicline (10–9 to 10-5M) showed increased intracellular calcium concentrations and an increase in expression of steroidogenic genes such as StAR CYP17A1, CYP21A2 and CYP11B2. Cell proliferation was not affected. Calcium entry into cells expressing the mutated nAChR receptor treated for 24h with increasing concentrations of Compound 9S (10–9 to 10-5M) induced an increase in expression of steroidogenic genes such as StAR, CYP21A2 and HSD3B2, but not CYP11B2. Similarly to the results obtained in cells expressing α7-5HT3, cell proliferation was unaffected in response to Compound 9S. These cell lines, in which we can modulate the intracellular calcium concentration « on demand », are a useful tool for a better understanding of the alterations of intracellular ion balance and calcium signaling in the pathophysiology of PA.

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