Ion Pumps Research Articles

D-Ribose-L-Cysteine Attenuated Polychlorinated Biphenyls Mediated Neuroendocrine-Transmembrane Ionic Pump ATPase Disruption and Peroxynitrite Formation in a Rat Model: A Possible Role of Testicular Antioxidant and Androgenic Enzymes

The very hazardous and persistent aquatic pollutants known as polychlorinated biphenyls (PCBs) are known to bioaccumulate in a range of marine mammals. Human and animal studies have shown that exposure to PCBs affects the male reproductive system. This study was conducted to investigate the therapeutic effects of D-ribose-L-cysteine (DRLC) on PCB-mediated ATPase disruption of the neuroendocrine transmembrane ion pump and peroxynitrite formation in rat models. After the first 15 days of PCB treatment, DRLC (50 mg/kg) was administered orally for 15 days, beginning on day 16 and continuing through day 30. PCB (2 mg/kg) was administered for 30 days. All tests were performed in accordance with accepted procedures. Kisspeptin (kissp), gonadotropin-releasing hormone alkaline phosphatase (ALP), lactate dehydrogenase (LDH), glutathione peroxidase (GSH-Px), and total antioxidant capacity (TAOC) were all analyzed in blood on day 31. The testes were also removed and sent for testosterone, testicular antioxidant enzymes (L-C and PrDx-4), androgenic enzymes (3β-HSD and 17β-HSD), sulfhydryl content, and transmembrane ion pump (Na+, K+, Ca2+, Mg2+, and H+ ions) The results of the study showed that Kisspeptin, GnRH, Testosterone, L-C, PrDx-4, 3-HSD, 17-HSD, HOST, Na+, K+, Ca2+, Mg2+, and H+-ATPase levels were significantly increased by DRLC. In addition, DRLC therapy dramatically reduced levels of ONOO-, H2O2, 8-OHdG, ALP, and LDH, while increasing TAOC to restore GSH-Px levels. The results of the present study suggest that DRLC is a potentially effective therapeutic approach to reduce PCB-induced neuroendocrine transmembrane ion pump disruption in an experimental rat model. The primary mechanism underlying this effect may be its antioxidant activities against the formation of peroxynitrite and elevated levels of hydrogen peroxide. HIGHLIGHTS DRLC abates PCBs-induced peroxynitrite stress in rats’ testes DRLC abates PCBs-induced sulphydryl depletion in rats’ testes DRLC ameliorated PCB-induced alteration in testicular ionic ATPase pumps DRLC enhances testicular antioxidant enzymes in rats treated with PCBs DRLC reversed PCB-induced decreased spermatogenesis in rats’ testes GRAPHICAL ABSTRACT

Light-Driven Chloride and Sulfate Pump with Two Different Transport Modes.

Ion pumps are membrane proteins that actively translocate ions by using energy. All known pumps bind ions in the resting state, and external energy allows ion transport through protein structural changes. The light-driven sodium-ion pump Krokinobacter eikastus rhodopsin 2 (KR2) is an exceptional case in which ion binding follows the energy input. In this study, we report another case of this unusual transport mode. The NTQ rhodopsin from Alteribacter aurantiacus (AaClR) is a natural light-driven chloride pump, in which the chloride ion binds to the resting state. AaClR is also able to pump sulfate ions, though the pump efficiency is much lower for sulfate ions than for chloride ions. Detailed spectroscopic analysis revealed no binding of the sulfate ion to the resting state of AaClR, indicating that binding of the substrate (sulfate ion) to the resting state is not necessary for active transport. This property of the AaClR sulfate pump is similar to that of the KR2 sodium pump. Photocycle dynamics of the AaClR sulfate pump resemble a non-functional cycle in the absence of anions. Despite this, flash photolysis and difference Fourier transform infrared spectroscopy suggest transient binding of the sulfate ion to AaClR. The molecular mechanism of this unusual active transport by AaClR is discussed.

Silencing of ATP1A1 attenuates cell membrane disruption by nanosecond electric pulses

This study explored the role of the Na/K-ATPase (NKA) in membrane permeabilization induced by nanosecond electric pulses. Using CRISPR/Cas9 and shRNA, we silenced the ATP1A1 gene, which encodes α1 NKA subunit in U937 human monocytes. Silencing reduced the rate and the cumulative uptake of YoPro-1 dye after electroporation by 300-ns, 7–10 kV/cm pulses, while ouabain, a specific NKA inhibitor, enhanced YoPro-1 entry. We conclude that the α1 subunit supports the electropermeabilized membrane state, by forming or stabilizing electropores or by hindering repair mechanisms, and this role is independent of NKA's ion pump function.

Optogenetic ion pumps differ with respect to the secondary pattern of K+ redistribution.

We recently reported that strong activation of the optogenetic chloride pump, halorhodopsin leads to a secondary redistribution of K+ ions into the cell, through tonically open, "leak" K+ channels. Here we show that this effect is not unique to halorhodopsin but is also seen with activation of another electrogenic ion pump, archaerhodopsin. The two opsins differ however in the size of the rebound rise in extracellular potassium, [K+ ]o , after the end of activation, which is far larger with halorhodopsin than for archaerhodopsin activation. Multiple linear regression modeling indicates that the variance in the postillumination surge in [K+ ]o was explained both by the size of the preceding, illumination-induced drop in [K+ ]o and also by the type of opsin. These data provide additional support for the hypothesis that intense chloride-loading of cells, as occurs naturally following intense bursts of GABAergic synaptic bombardment, or artificially following halorhodopsin activation, is followed by extrusion of both Cl- and K+ coupled together. We discuss this with respect to the pattern of [K+ ]o rise that occurs at the onset of seizure-like events.

Model Analysis of Post-Stimulation Block of a Myelinated Axon by Direct Current.

To determine the role of ion concentrations and ion pump activity in conduction block of myelinated axon induced by a long-duration direct current (DC). A new axonal conduction model for myelinated axons based on the classical Frankenhaeuser-Huxley (FH) equations is developed that includes ion pump activity and allows the intracellular and extracellular Na+ and K+ concentrations to change with axonal activity. Action potential generation, propagation, and acute DC block occurring within a short period (milliseconds) that do not significantly change the ion concentrations or trigger ion pump activity are successfully simulated by the new model in a similar way as the classical FH model. Different from the classical model, the new model also successfully simulates the post-stimulation block phenomenon, i.e., the axonal conduction block occurring after terminating a long-duration (30 seconds) DC stimulation as observed recently in animal studies. The model reveals a significant K+ accumulation outside the axonal node as the possible mechanism underlying the post-DC block that is slowly reversed by ion pump activity during the post-stimulation period. Changes in ion concentrations and ion pump activity play an important role in post-stimulation block induced by long-duration DC stimulation. Long-duration stimulation is used clinically for many neuromodulation therapies, but the effects on axonal conduction/block are poorly understood. This new model will be useful for better understanding of the mechanisms underlying long-duration stimulation that changes ion concentrations and triggers ion pump activity.

Roundup® disrupts tissue architecture, attenuates Na+/K+-ATPase expression, and induces protein oxidation/nitration, cellular apoptosis, and antioxidant enzyme expressions in the gills of goldfish, Carassius auratus

Extensive agricultural activities to feed the growing population are one major driving force behind aquatic pollution. Different types of pesticides are used in farmlands to increase crop production and wash up into water bodies. Glyphosate-based herbicide Roundup® is one of the most used pesticides in the United States; however, its effects on teleost species are still poorly understood. This study focused on the effects of environmentally relevant concentrations of Roundup exposure (low- and high-dose: 0.5 and 5 μg/L for 2-week) on Na+/K+-ATPase (NKA, a biomarker for sodium‑potassium ion pump efficacy), cytochrome P450-1A (CYP1A, a monooxygenase enzyme), 2,4-dinitrophenyl protein (DNP, a biomarker for protein oxidation), 3-nitrotyrosine protein (NTP, a biomarker for protein nitration), superoxidase dismutase (SOD, an antioxidant enzyme), catalase (CAT, an antioxidant enzyme) expressions, and cellular apoptosis in the gills of goldfish. Histopathological and in situ TUNEL analyses showed widespread tissue damage, including lamellar fusion, loss of gill architecture, club shape of primary lamellae, mucous formation, and distortion in the epithelium layer, as well as apoptotic nuclei in gills. Immunohistochemical and qRT-PCR analyses provided insights into the expressions of molecular indicators in gills. Fish exposed to Roundup exhibited a significant (P < 0.05) downregulation of NKA expression in gills. Additionally, we observed upregulation of CYP1A, DNP, NTP, SOD, and CAT expressions in the gills of goldfish. Overall, our results suggest that exposure to Roundup causes disruption of gill architecture, induces protein oxidation/nitration and cellular apoptosis, and alters prooxidant-antioxidant homeostasis in tissues, which may lead to reduced fitness and survivability of teleost species.

Zeolitic imidazolate framework/aptamer-based fluorescence assay for the facile and high-sensitivity detection of acetamiprid

Accurate monitoring of trace pesticides in complex matrix remains a challenge in food safety supervision. Herein, we designed a facile zeolitic imidazolate framework (ZIF)-8/aptamer-based assay for the sensitive detection of acetamiprid. ZIF-8 efficiently adsorbs 6-carboxyfluorescein-labeled complementary DNA (cDNA-FAM) via electrostatic interaction, hydrogen bonding and Zn2+ coordination, which contributed to resistance to cDNA-FAM displacement by biological ligands. ZIF-8 serves as an “ion pump” that contains lots of Zn2+ who boosts cDNA-FAM adsorption and triggers the photoinduced electron transfer (PET) effect from FAM to ZIF-8, improving the sensing sensitivity. Acetamiprid could trigger the change in the adsorption state of cDNA-FAM, further tuning the PET effect and causing fluorescence conversion. The fluorescence assay showed a high sensitivity for monitoring acetamiprid with a detection limit of 0.05 ng mL−1 in the apple sample. This ZIF/DNA-based analytical platform provides a powerful tool for facile and low-cost screening of pesticide residues, with promising applications in food safety monitoring.

Mechanisms of Nutrient Uptake and Assimilation Processes in Some Plants: A Review

Nutrient demands of plants are fulfilled via nutrient uptake by the roots, even though minor quantities of certain nutrients might be assimilated via leaves. For the reason that the majority of nutrients are assimilated by roots, an understanding of root morphology and cell structure is crucial in knowing this basic plant process. Nutrient achievement by plants hinges on ion applications on superficial, root assimilation capacity, and plant requirement. Movement of ion in plant cells is classified into active and passive. Ion concentrations in the cytoplasm of plant cells are frequently and considerably observed to be greater than in soil solutions. Consequently, roots ought to be able to take up ions in contrast to broadly diverse concentration gradients. Currently, two major theories of ion transport across membranes are reported in literature: carrier theory where carrier agents accountable for transferring ions from one side of membrane to the other; encounter specific ions for which they have attraction, form carrier ion complexes; and move across membranes and connecting ATPase theory of ion transport; which is related with the plasmalemma and is activated by cations; the ion pump theory, which is a demanding proces, transporting via electrochemical gradient. Measurements of ion uptake could be achieved through tracer techniques. Long-distance transport of ions to shoots happens in the vascular system, with water being the transporting agent. New and stimulating developments in mineral uptake mechanism of plants have momentously added to our understanding of the function of nutrients uptake in plants. Most research comparative to physiology of nutrient uptake has been conducted under controlled environment by means of particular nutrient cultures in the growth medium.

Demystifying the Venus flytrap action potential.

All plants are electrically excitable, but only few are known to fire a well-defined, all-or-nothing action potential (AP). The Venus flytrap Dionaea muscipula displays APs with an extraordinarily high firing frequency and speed, enabling the capture organ of this carnivorous plant to catch small animals as fast as flies. The number of APs triggered by the prey is counted and serves as the basis for decisions within the flytrap's hunting cycle. The archetypical Dionaea AP lasts 1 s and consists of fivephases: Starting from the resting state, an initial cytosolic Ca2+ transient is followed by depolarization, repolarization and a transient hyperpolarization (overshoot) before the original membrane potential is finally recovered. When the flytrap matures and becomes excitable, a distinct set of ion channels, pumps and carriers is expressed, each mastering a distinct AP phase.

The FSH–mTOR–CNP signaling axis initiates follicular antrum formation by regulating tight junction, ion pumps, and aquaporins

The initial formation of the follicular antrum (iFFA) serves as a dividing line between gonadotropin-independent and gonadotropin-dependent folliculogenesis, enabling the follicle to sensitively respond to gonadotropins for its further development. However, the mechanism underlying iFFA remains elusive. Herein, we reported that iFFA is characterized by enhanced fluid absorption, energy consumption, secretion, and proliferation, and shares a regulatory mechanism with blastula cavity formation. By use of bioinformatics analysis, follicular culture, RNA interference, and other techniques, we further demonstrated that the tight junction, ion pumps, and aquaporins are essential for follicular fluid accumulation during iFFA, as a deficiency of any one of these negatively impacts fluid accumulation and antrum formation. The intra-ovarian mTOR-CNP pathway, activated by FSH, initiated iFFA by activating tight junction, ion pumps, and aquaporins. Building on this, we promoted iFFA by transiently activating mTOR in cultured follicles and significantly increased oocyte yield. These findings represent a significant advancement in iFFA research, further enhancing our understanding of folliculogenesis in mammals.

Bioelectric regulation of intestinal stem cells.

Proper regulation of ion balance across the intestinal epithelium is essential for physiological functions, while ion imbalance causes intestinal disorders with dire health consequences. Ion channels, pumps, and exchangers are vital for regulating ion movements (i.e., bioelectric currents) that control epithelial absorption and secretion. Recent in vivo studies used the Drosophila gut to identify conserved pathways that link regulators of Ca2+, Na+ and Cl- with intestinal stem cell (ISC) proliferation. These studies laid a foundation for using the Drosophila gut to identify conserved proliferative responses triggered by bioelectric regulators. Here, we review these studies, discuss their significance, as well as the advantages of using Drosophila to unravel conserved bioelectrically induced molecular pathways in the intestinal epithelium under physiological, pathophysiological, and regenerative conditions.

Incoherent pumping field and Er3+ ion concentration effects on diffraction pattern of transmitted light in Er3+ doped YAG crystal

The effect of Er[Formula: see text] ion concentration and incoherent pumping field on the Fraunhofer diffraction pattern of the transmitted light beam in Er[Formula: see text]: YAG crystal is discussed. It is shown that under different concentration of Er[Formula: see text] ion in crystal, the energy of the probe light can transfer to the higher orders of the grating. Also, it is shown that the switching from electromagnetically induced grating to electromagnetically induced phase gratin or vice versa can be obtained by different concentration of Er[Formula: see text] ion and incoherent pumping rate in crystal. Moreover, we have found that by replacing the probe light by optical vortex light, the asymmetric diffraction pattern can be obtained by tuning the optical vorticity of optical vortex light. In this case, the asymmetric diffraction pattern can also be controlled at different ion concentration.

Flexible Organic Electronic Ion Pump Fabricated Using Inkjet Printing and Microfabrication for Precision In Vitro Delivery of Bupivacaine.

The organic electronic ion pump (OEIP) is an on-demand electrophoretic drug delivery device, that via electronic to ionic signal conversion enables drug delivery without additional pressure or volume changes. The fundamental component of OEIPs is their polyelectrolyte membranes which are shaped into ionic channels that conduct and deliver ionic drugs, with high spatiotemporal resolution. The patterning of these membranes is essential in OEIP devices and is typically achieved using laborious microprocessing techniques. Here, the development of an inkjet printable formulation of polyelectrolyte is reported, based on a custom anionically functionalized hyperbranched polyglycerol (i-AHPG). This polyelectrolyte ink greatly simplifies the fabrication process and is used in the production of free-standing OEIPs on flexible polyimide (PI) substrates. Both i-AHPG and the OEIP devices are characterized, exhibiting favorable iontronic characteristics of charge selectivity and the ability to transport aromatic compounds. Further, the applicability of these technologies is demonstrated by the transport and delivery of the pharmaceutical compound bupivacaine to dorsal root ganglion cells with high spatial precision and effective nerve blocking, highlighting the applicability of these technologies for biomedical scenarios.

Coevolutionary escalation led to differentially adapted paralogs of an insect's Na,K-ATPase optimizing resistance to host plant toxins.

Cardiac glycosides are chemical defence toxins known to fatally inhibit the Na,K-ATPase (NKA) throughout the animal kingdom. Several animals, however, have evolved target-site insensitivity through substitutions in the otherwise highly conserved cardiac glycoside binding pocket of the NKA. The large milkweed bug, Oncopeltus fasciatus, shares a long evolutionary history with cardiac glycoside containing plants that led to intricate adaptations. Most strikingly, several duplications of the bugs' NKA1α gene provided the opportunity for differential resistance-conferring substitutions and subsequent sub-functionalization of the enzymes. Here, we analysed cardiac glycoside resistance and ion pumping activity of nine functional NKA α/β-combinations of O. fasciatus expressed in cell culture. We tested the enzymes with two structurally distinct cardiac glycosides, calotropin, a host plant compound, and ouabain, a standard cardiac glycoside. The identity and number of known resistance-conferring substitutions in the cardiac glycoside binding site significantly impacted activity and toxin resistance in the three α-subunits. The β-subunits also influenced the enzymes' characteristics, yet to a lesser extent. Enzymes containing the more ancient αC-subunit were inhibited by both compounds but much more strongly by the host plant toxin calotropin than by ouabain. The sensitivity to calotropin was diminished in enzymes containing the more derived αB and αA, which were only marginally inhibited by both cardiac glycosides. This trend culminated in αAβ1 having higher resistance against calotropin than against ouabain. These results support the coevolutionary escalation of plant defences and herbivore tolerance mechanisms. The possession of multiple paralogs additionally mitigates pleiotropic effects by compromising between ion pumping activity and resistance.

Evaluation of dosimetric parameters after electron gun and ion pump replacement in linear accelerator device and comparison of results by gATE/Geant4 simulation

This study evaluates dosimetric data such as PDD, dose profile and tissue phantom rate (TPR20/10) after replacing the LINAC device's electron gun and ion chamber pump. These values obtained after the change were compared with the standard PDD protocol, British Journal of Radiology Supplement 25 (BJR 25) report, Beam Data (measured and recorded as reference values during the setup phase, BD) and simulation results. In additional, uncertainty results were obtained for absorbed doses to water using different calculation tools. The experimental setup was created in the GATE/Geant4 simulation program, and the experimentally obtained TPR20/10, beam profile and PDD values were compared with the simulation. The difference between TPR20/10 values for 6 and 18 MV photon energies was found to be below 1% for 6 MVs and 3% for 18 MV. When different calculation tools were used, uncertainties were found in the absorbed dose measurements ranging between 0.8% and 1.87%, which is compatible with the uncertainties (1.4-2.1%) specified in the IAEA report. Even though small uncertainties were observed in the results, the differences between the calculations in the measurements of absorbed doses were insignificant. Estimated uncertainties for GATE was a little smaller than those measured using experimental methods, BD and BJR 25. Although the values obtained are within the tolerance, after such significant materials are changed in the LINAC device, a water phantom should be set up, the measurements should be repeated, and the results should be confirmed to be within the limit values.

How Might Consideration of Cell Polarity Affect Daily Therapeutic Practices?A Literature Review:.

In addition to biochemical gradients and transcriptional networks, cell behaviour is controlled by endogenous bioelectrical signals resulting from the action of ion channels and pumps. Cells are regulated not only by their own membrane resting potential (Vmem) but also by the Vmem of neighbouring cells, establishing networks through electrical synapses known as gap junctions. V mem is the primary factor in producing a polarity that can regulate cell assimilation of various substances. This article aimed to examine how cell polarity can change and how variations in cell polarity may lead to clinical demonstrations. Using Cochrane Central, PubMed, Scopus, Web of Science (WOS), and Embase, a comprehensive qualitative literature review was conducted from February 1, 2018, to February 1, 2023, to identify studies addressing bioelectric, cell polarity, and electroceuticals in patients with foot and ankle problems. Out of 1,281 publications, 27 were included. One study investigated bioelectric wound-healing. Twenty-five studies examined bioelectric nerve cell growth, whereas one study evaluated bioelectricity-induced cellular differentiation in the treatment of arteriopathies. The author of this systematic review support addressing the predisposing factors and healing impediments for a disease, thereby enhancing the healing process and reducing the likelihood of recurrence or parallel conditions. This method of treatment has provided a summary of evidence indicating that cell polarity could be addressed for the treatment and prevention of most if not all, foot and ankle problems. However, owing to the limitations of V mem and bioelectricity measurement and the direct or indirect involvement of genetics and chemical gradients, further studies are required to confirm these results.

Recent upgrades and developments at TRIUMF’s laser nuclear-spin-polarization facility

By collinearly laser optical pumping of atoms and ions, the laser nuclear-spin-polarization beam facility at TRIUMF-ISAC has successfully provided highly nuclear-spin polarized radioactive isotope beams, such as 8Li and 31Mg, to study material science, biochemistry, nuclear physics, and fundamental symmetries for over 20 years. In recent years with emerging research in all these fields using β-decay asymmetry of polarized nuclei, more novel/exotic species need to be laser-polarized, such as 230,232Ac and 58,74Cu. To develop optical pumping schemes and provide novel nuclear-spin polarized beams to meet these increasing demands the classical ISAC polarizer facility requires upgrades. In this paper, an overview of the polarizer facility is presented and recent, as well as ongoing, upgrades and development work are discussed.

The Importance of Electrode Material in Bioelectronic Electrophoretic Ion Pumps

AbstractBioelectronic ion pumps deliver ions and biomolecules from a source to a target biological system with high spatiotemporal control for bioengineering and regenerative medicine applications. A voltage between a working electrode and a reference/counter electrode delivers the charged ions and biomolecules from a source to the desired target. The source and the target are separated by an ion exchange membrane so that only the charged molecules of interest are delivered. Future wearable and implantable applications require high efficiency of delivery to minimize power consumption. The majority of recent efforts on improving ion pump efficiency have focused on optimizing the ion exchange membrane. However, the contribution of the working electrode material to the ion pump efficiency has been mostly overlooked. This work identifies how changing the working electrode material greatly affects the efficiency of delivery in ion pumps. With an electrical circuit model analysis, voltammetry studies on silver, platinum, and palladium hydride working electrodes, and implementation of the Butler–Volmer equation, results show that the material‐dependent equilibrium potential at the working electrode surface has a large impact on ion pump efficiency. With this knowledge, a simple predictive model to optimize the working electrode material for delivering each specific ion or molecule of interest is designed.

Structure and Heterogeneity of Retinal Chromophore in Chloride Pump Rhodopsins Revealed by Raman Optical Activity.

Chloride transport by microbial rhodopsins is actively being researched to understand how light energy is converted to drive ion pumping across cell membranes. Chloride pumps have been identified in archaea and eubacteria, and there are similarities and differences in the active site structures between these groups. Thus, it has not been clarified whether a common mechanism underlies the ion pump processes for all chloride-pumping rhodopsins. Here, we applied Raman optical activity (ROA) spectroscopy to two chloride pumps, Nonlabens marinus rhodopsin-3 (NM-R3) and halorhodopsin from the cyanobacterium Mastigocladopsis repens (MrHR). ROA is a vibrational spectroscopy that provides chiral sensitivity, and the sign of ROA signals can reveal twisting of cofactor molecules within proteins. Our ROA analysis revealed that the retinal Schiff base NH group orients toward the C helix and forms a direct hydrogen bond with a nearby chloride ion in NM-R3. In contrast, MrHR is suggested to contain two retinal conformations twisted in opposite directions; one conformation has a hydrogen bond with a chloride ion like NM-R3, while the other forms a hydrogen bond with a water molecule anchored by a G helix residue. These results suggest a general pump mechanism in which the chloride ion is "dragged" by the flipping Schiff base NH group upon photoisomerization.

Modulation of calcium signaling “on demand” to decipher the molecular mechanisms responsible for primary aldosteronism

Primary aldosteronism (PA) is the most frequent form of secondary hypertension. Over the past two decades, major advances have been made in our understanding of the disease with the identification of germline or somatic mutations in ion channels and pumps. These mutations enhance calcium signaling, the main trigger of aldosterone biosynthesis. The objective of our work was to elucidate, using chemogenetic tools, the molecular mechanisms underlying the development of PA by modulating sodium entry into the cells, thus mimicking some of the known mutations identified in PA. We have developed an adrenocortical H295R-S2 cell line stably expressing a chimeric ion channel receptor formed by the extracellular ligand-binding domain of the a7 nicotinic acetylcholine receptor fused to the ion pore domain of the serotonin receptor 5HT3a named a7-5HT3. Its activation by a selective agonist named PSEM-817 leads to sodium entry into the cells. This cell line was characterized in terms of intracellular sodium and calcium concentrations, cell proliferation, steroid production electrophysiological properties, and gene expression. Treatment of a7-5HT3 expressing cells with increasing concentration of PSEM-817 (from 10–9 to 10–5 M) induced a significant increase in intracellular calcium concentrations. Interestingly, whereas cells were hyperpolarized in absence of stimulation (around –60 mV), PSEM-817 induced a strong depolarization, with cells rising to a membrane potential of around –10 mV. The stimulation of calcium signaling by PSEM-817 leads to an increase of CYP11B2 (encoding for aldosterone synthase) mRNA expression and aldosterone biosynthesis but did not affect cell proliferation measured at different time points (8 h, 24 h, 48 h, 72 h). Interestingly, calcium kinetic analyses revealed significant differences in response to the modulation of potassium or sodium entry into cells. Gene expression analyses of gene expression by RNAseq highlighted the activation of specific signaling pathways in response to treatment with Angiotensin II, potassium, and PSEM-817. This cell line, in which we can modulate the intracellular calcium concentration “on demand”, is a useful tool for a better understanding of the alterations of intracellular ion balance and calcium signaling in the pathophysiology of PA.