Identification of Voltage‐Activated Na<sup>+</sup> and K<sup>+</sup> Channels in Human Steroid‐Secreting Ovarian Cells

Bulling, Andreas; Brucker, Cosima; Berg, U.; Gratzl, Manfred; Mayerhofer, Artur

doi:10.1111/j.1749-6632.1999.tb11275.x

Cited by 15 publications

(6 citation statements)

References 8 publications

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“…Currently, little is known about the ion channels expressed by ovarian cells and human GCs, in particular. However, we found that human GCs express Na ϩ and K ϩ channels (Bulling et al, 1999. Using electrophysiological approaches, our laboratory has obtained preliminary data indicating that specific K ϩ currents (Kunz et al, unpublished data), as well as gap junctional communication, can be regulated by cholinergic drugs (Fritz et al, 2002).…”

Section: Ongoing Research Future Goals and Conclusionmentioning

confidence: 96%

Ovarian acetylcholine and muscarinic receptors: Hints of a novel intrinsic ovarian regulatory system

Mayerhofer

Fritz

2002

Microscopy Res & Technique

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More than two decades ago, the degrading enzyme of the neurotransmitter acetylcholine (ACH) was reported in nerve fibers of the rat ovary. Subsequently, it was assumed that ACH is a neurotransmitter of ovarian nerves, although the sole presence of the degrading enzyme, ACH-esterase, does not allow such a conclusion. That ACH may be involved in the complex regulation of ovarian functions, including hormone production, was indicated by studies using, for example, granulosa cells (GCs). The lack of detailed information about both source(s) and functions of ACH in the ovary prompted us to examine sites of ovarian ACH-synthesis and ACH-receptor-bearing target cells. We also started to identify functions of ACH in cultured human GCs. While ovarian innervation and recently described neuron-like cells of the ovary were not immunoreactive for the ACH-synthesizing enzyme, choline-acetyl transferase (CHAT), we found immunoreactivity in GCs of rodents and primates. Isolated human and rat GCs produced ACH and contained the vesicular ACH transporter (VACHT). These results indicate that endocrine GCs are an unexpected non-neuronal source of ACH in the ovary. Moreover, these cells and GCs in vivo contain ACH-receptors of the muscarinic subtype (MR), namely M1R and M5R. In contrast, oocytes express M3R. MR of human GCs are functional and cholinergic stimulation is linked to rapid increases in intracellular Ca(++) levels. M1/5R activation also led to increased cell proliferation of human GCs in vitro and this stimulatory effect was found to be associated with rapid disruption of gap junction communication. Ongoing studies begin to identify regulation of ion channels and altered gene expression as consequences of MR stimulation. Thus, our results outline first details of an unexpected intraovarian, non-neuronal cholinergic system, and suggest that it may be involved in the regulation of cell proliferation in the ovary.

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Section: Ongoing Research Future Goals and Conclusionmentioning

confidence: 96%

Ovarian acetylcholine and muscarinic receptors: Hints of a novel intrinsic ovarian regulatory system

Mayerhofer

Fritz

2002

Microscopy Res & Technique

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“…There is also another sodium-calcium exchanger (NcX) where ion exchange leads to changes in intracellular calcium ion concentration and PH as well as changes in the cellular microenvironment. The altered calcium ion concentration promotes the formation of pedicles/endopods, which indirectly affects the cell migration and metastasis process (41)(42)(43). Among the results of virtual screening based on the structure of ScN8A, T0950 (trade name Neomycin sulfate) is an FdA-approved aminoglycoside antibiotic and phospholipase c inhibitor known to be commercially available.…”

Section: Discussionmentioning

confidence: 99%

Role of the voltage‑gated sodium channel Nav1.6 in glioma and candidate drugs screening

Zhang

et al. 2023

Int J Mol Med

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Gliomas remain a clinical challenge, common and fatal. Treatment of glioblastoma remains elusive, and researchers have focused on discovering new mechanisms and drugs. It has been well established that the expression of voltage-gated sodium channels (VGScs) is abnormally increased in numerous malignancies and, in general, is rarely expressed in the corresponding normal tissues. This suggests that ion channel activity appears to be associated with malignant progression of tumors. VGScs remain largely unknown as to how their activity leads to an increase in cancer cell activity or invasiveness. certain sodium ion channel subtypes (for instance, Nav1.5 and Nav1.7) are associated with metastasis and invasion in cancers including breast and colorectal cancers. A previous study by the authors explored the expression of certain ion channels in glioma, but there are few studies related to Nav1.6. The current study aimed to elucidate the expression and role of Nav1.6 in glioma and to screen potential drugs for the treatment of glioma by virtual screening and drug sensitivity analysis. Nav1.6 relative expression of mRNA and protein was determined by reverse transcription-quantitative PcR and western blot analysis. cell proliferation was determined by cell counting Kit-8 assay. cell migration was assessed by cellular wound healing assay. cell invasion and apoptosis were detected by Transwell cell invasion assay and flow cytometry. Last but not least, FDA-approved drugs were screened using virtual screening, molecular docking and NcI-60 drug sensitivity analyses based on the expression and structure of Nav1.6. In glioma cells, Nav1.6 was significantly upregulated and expressed mostly in the cytoplasm and cell membrane; its expression was positively correlated with pathological grade. A172 and U251 cells exhibited reduced proliferation, migration and invasion when Nav1.6 expression was knocked down, and apoptosis was increased. TNF-α (100 pg/ml) acting on glioma cells was found to upregulate the expression level of Nav1.6, and TNF-α was involved in the process of Nav1.6 promoting malignant progression of glioma. Finally, certain FDA-approved drugs were identified by virtual screening and drug sensitivity analysis. In conclusion, the present study demonstrated the expression and role of Nav1.6 in glioma and identified several FDA-approved drugs that are highly correlated with Nav1.6 and could be candidate drugs for patients with glioma.

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“…VGSC are responsible for action potential initiation and propagation in nerve, muscle and neuroendocrine cell types (Diaz et al, 2007); however, they are also expressed in nonexcitable cells like steroid-secreting ovarian cells (Bulling et al, 1999). VGSC consist of a single protein chain, the a subunit, which is associated with auxiliary proteins or b subunits.…”

Section: Sodium Channelsmentioning

confidence: 99%

Ion channels in toxicology

Restrepo-Angulo

Vizcaya-Ruiz

Camacho

2010

J of Applied Toxicology

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Ion channels play essential roles in human physiology and toxicology. Cardiac contraction, neural transmission, temperature sensing, insulin release, regulation of apoptosis, cellular pH and oxidative stress, as well as detection of active compounds from chilli, are some of the processes in which ion channels have an important role. Regulation of ion channels by several chemicals including those found in air, water and soil represents an interesting potential link between environmental pollution and human diseases; for instance, de novo expression of ion channels in response to exposure to carcinogens is being considered as a potential tool for cancer diagnosis and therapy. Non-specific binding of several drugs to ion channels is responsible for a huge number of undesirable side-effects, and testing guidelines for several drugs now require ion channel screening for pharmaceutical safety. Animal toxins targeting human ion channels have serious effects on the population and have also provided a remarkable tool to study the molecular structure and function of ion channels. In this review, we will summarize the participation of ion channels in biological processes extensively used in toxicological studies, including cardiac function, apoptosis and cell proliferation. Major findings on the adverse effects of drugs on ion channels as well as the regulation of these proteins by different chemicals, including some pesticides, are also reviewed. Association of ion channels and toxicology in several biological processes strongly suggests these proteins to be excellent candidates to follow the toxic effects of xenobiotics, and as potential early indicators of life-threatening situations including chronic degenerative diseases.

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Identification of Voltage‐Activated Na⁺ and K⁺ Channels in Human Steroid‐Secreting Ovarian Cells

Cited by 15 publications

References 8 publications

Ovarian acetylcholine and muscarinic receptors: Hints of a novel intrinsic ovarian regulatory system

Ovarian acetylcholine and muscarinic receptors: Hints of a novel intrinsic ovarian regulatory system

Role of the voltage‑gated sodium channel Nav1.6 in glioma and candidate drugs screening

Ion channels in toxicology

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Identification of Voltage‐Activated Na+ and K+ Channels in Human Steroid‐Secreting Ovarian Cells

Cited by 15 publications

References 8 publications

Ovarian acetylcholine and muscarinic receptors: Hints of a novel intrinsic ovarian regulatory system

Ovarian acetylcholine and muscarinic receptors: Hints of a novel intrinsic ovarian regulatory system

Role of the voltage‑gated sodium channel Nav1.6 in glioma and candidate drugs screening

Ion channels in toxicology

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Identification of Voltage‐Activated Na⁺ and K⁺ Channels in Human Steroid‐Secreting Ovarian Cells