Pro-Reparative Effects of KvLQT1 Potassium Channel Activation in a Mouse Model of Acute Lung Injury Induced by Bleomycin.

Acute Respiratory Distress Syndrome (ARDS) is a complex and devastating form of respiratory failure, with high mortality rates, for which there is no pharmacological treatment. The acute exudative phase of ARDS is characterized by severe damage to the alveolar-capillary barrier, infiltration of protein-rich fluid into the lungs, neutrophil recruitment, and high levels of inflammatory mediators. Rapid resolution of this reversible acute phase, with efficient restoration of alveolar functional integrity, is essential before the establishment of irreversible fibrosis and respiratory failure.

The 33 Ion Channels Meeting, September 2024, Sète, France.

The 33 Ion Channels Meeting has been held in Sète, France, from September 8 to 11. The congress gathered together senior and junior researchers from almost all over the world working on different fields of biology and pathophysiology. The colloquium opened with the plenary lecture on the action mechanisms of α2δ proteins in the trafficking of calcium channels and how these proteins can modulate the channels functional properties, given by Prof.

The 32nd Ion Channels Meeting, 17th-20th September 2023, Sète, France.

The 32nd Ion Channel Meetings were organized by the Ion Channels Association from September 17 to 20, 2023 in the Occitanie region (Sète). Researchers, post-docs and students from France, Europe and non-European countries came together to present and discuss their work on various themes covering the field of neuroscience, stem cells, hypoxia and pathophysiology cardiac. Through the plenary conference given by Professor Emilio Carbone and the 5 conferences organized by the scientific committee, attention was paid this year to autism, neuromotor and cardiac disorders and tumor aggressive processes.

Function of KvLQT1 potassium channels in a mouse model of bleomycin-induced acute lung injury.

Acute respiratory distress syndrome (ARDS) is characterized by an exacerbated inflammatory response, severe damage to the alveolar-capillary barrier and a secondary infiltration of protein-rich fluid into the airspaces, ultimately leading to respiratory failure. Resolution of ARDS depends on the ability of the alveolar epithelium to reabsorb lung fluid through active transepithelial ion transport, to control the inflammatory response, and to restore a cohesive and functional epithelium through effective repair processes. Interestingly, several lines of evidence have demonstrated the important role of potassium (K) channels in the regulation of epithelial repair processes.

Impact of KvLQT1 potassium channel modulation on alveolar fluid homeostasis in an animal model of thiourea-induced lung edema.

Alveolar ion and fluid absorption is essential for lung homeostasis in healthy conditions as well as for the resorption of lung edema, a key feature of acute respiratory distress syndrome. Liquid absorption is driven by active transepithelial sodium transport, through apical ENaC Na channels and basolateral Na/K-ATPase. Our previous work unveiled that KvLQT1 K channels also participate in the control of Na/liquid absorption in alveolar epithelial cells.

Acid Adaptation Promotes TRPC1 Plasma Membrane Localization Leading to Pancreatic Ductal Adenocarcinoma Cell Proliferation and Migration through Ca Entry and Interaction with PI3K/CaM.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with a low overall survival rate of less than 10% and limited therapeutic options. Fluctuations in tumor microenvironment pH are a hallmark of PDAC development and progression. Many ion channels are bona fide cellular sensors of changes in pH.

The TRPC1 Channel Forms a PI3K/CaM Complex and Regulates Pancreatic Ductal Adenocarcinoma Cell Proliferation in a Ca-Independent Manner.

Dysregulation of the transient receptor canonical ion channel (TRPC1) has been found in several cancer types, yet the underlying molecular mechanisms through which TRPC1 impacts pancreatic ductal adenocarcinoma (PDAC) cell proliferation are incompletely understood. Here, we found that TRPC1 is upregulated in human PDAC tissue compared to adjacent pancreatic tissue and this higher expression correlates with low overall survival. TRPC1 is, as well, upregulated in the aggressive PDAC cell line PANC-1, compared to a duct-like cell line, and its knockdown (KD) reduced cell proliferation along with PANC-1 3D spheroid growth by arresting cells in the G1/S phase whilst decreasing cyclin A, CDK2, CDK6, and increasing p21 expression.

The N and C-termini of SPCA2 regulate differently Kv10.1 function: role in the collagen 1-induced breast cancer cell survival.

It's now clearly established that the tumor microenvironment participates to tumor development. Among the different actors contributing to these processes, ion channels, located at the cancer cell surface, play a major role. We recently demonstrated that the association of Kv10.

Effects of the Tumor Environment on Ion Channels: Implication for Breast Cancer Progression.

In recent years, it has been shown that breast cancer consists not only of neoplastic cells, but also of significant alterations in the surrounding stroma or tumor microenvironment. These alterations are now recognized as a critical element for breast cancer development and progression, as well as potential therapeutic targets. Furthermore, there is no doubt that ion channels are deregulated in breast cancer and some of which are prognostic markers of clinical outcome.

Roles for Ca and K channels in cancer cells exposed to the hypoxic tumour microenvironment.

For twenty years, ion channels have been studied in cancer progression. Several information have been collected about their involvement in cancer cellular processes like cell proliferation, motility and their participation in tumour progression using in-vivo models. Tumour microenvironment is currently the focus of many researches and the highlighting of the relationship between cancer cells and surrounding elements, is expanding.

Enhancing Nab-Paclitaxel Delivery Using Microbubble-Assisted Ultrasound in a Pancreatic Cancer Model.

A combination of microbubbles (MBs) and ultrasound (US) is an emerging method for noninvasive and targeted enhancement of anti-cancer drug uptake. This method showed an increase local drug extravasation in tumor tissue while reducing the systemic adverse effects in various tumor models. The present study aims to evaluate the effectiveness of this approach for Nab-paclitaxel delivery in a pancreatic tumor model.

Ion Channels: New Actors Playing in Chemotherapeutic Resistance.

In the battle against cancer cells, therapeutic modalities are drastically limited by intrinsic or acquired drug resistance. Resistance to therapy is not only common, but expected: if systemic agents used for cancer treatment are usually active at the beginning of therapy (i.e.

Original association of ion transporters mediates the ECM-induced breast cancer cell survival: Kv10.1-Orai1-SPCA2 partnership.

In the last years it has been shown that many components of tumor microenvironment (TM) can induce cell signaling that permit to breast cancer cells (BC) to maintain their aggressiveness. Ion channels have a role in mediating TM signal; recently we have demonstrated a functional collaboration between Kv10.1 and Orai1 channels in mediating the pro-survival effect of collagen 1 on BC cells.

Possible association of CAG repeat polymorphism in KCNN3 encoding the potassium channel SK3 with oxaliplatin-induced neurotoxicity.

Introduction: Data suggest a role of the potassium channel SK3 (KCNN3 gene) in oxaliplatin-induced neurotoxicity (OIN). Length variations in the polymorphic CAG repeat of the KCNN3 gene may be associated with the risk of OIN.

Materials And Methods: We performed patch-clamp experiments on HEK293 cell lines, expressing SK3 channel isoforms with short (11) or long (24) CAG repetitions, to measure intracellular calcium concentrations to test the effects of oxaliplatin on current density.

Monoclonal Antibodies Targeting the IL-17/IL-17RA Axis: An Opportunity to Improve the Efficiency of Anti-VEGF Therapy in Fighting Metastatic Colorectal Cancer?

Colorectal cancer is a major problem for public health worldwide because of its frequency and its severity. Many efforts have been carried to target the vascular endothelial growth factor (VEGF) pathway, one of the main promoters of pathological angiogenesis. Therapeutic monoclonal antibodies against VEGF have emerged as essential biopharmaceuticals for the advanced stages of the disease, in association with appropriate backbone chemotherapy.

A possible association of baseline serum IL-17A concentrations with progression-free survival of metastatic colorectal cancer patients treated with a bevacizumab-based regimen.

Background: Colorectal cancer is a major public health issue worldwide. Interleukin-17 (IL-17) and Th17 (T-helper cell type 17)-related molecules are involved in tumor development and in resistance to bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody used in association with chemotherapy in metastatic colorectal cancer. Some studies have previously shown that IL-17A and IL-17F polymorphisms, respectively rs2275913 and rs763780, are associated with gastric or colorectal cancer risk.

Complementary roles of KCa3.1 channels and β1-integrin during alveolar epithelial repair.

Background: Extensive alveolar epithelial injury and remodelling is a common feature of acute lung injury and acute respiratory distress syndrome (ARDS) and it has been established that epithelial regeneration, and secondary lung oedema resorption, is crucial for ARDS resolution. Much evidence indicates that K(+) channels are regulating epithelial repair processes; however, involvement of the KCa3.1 channels in alveolar repair has never been investigated before.

Identification of KvLQT1 K+ channels as new regulators of non-small cell lung cancer cell proliferation and migration.

K+ channels, which are overexpressed in several cancers, have been identified as regulators of cell proliferation and migration, key processes in cancer development/propagation. Their role in lung cancer has not been studied extensively; but we showed previously that KvLQT1 channels are involved in cell migration, proliferation and repair of normal lung epithelial cells. We now investigated the role of these channels in lung cancer cell lines and their expression levels in human lung adenocarcinoma (AD) tissues.

Evidence of K+ channel function in epithelial cell migration, proliferation, and repair.

Efficient repair of epithelial tissue, which is frequently exposed to insults, is necessary to maintain its functional integrity. It is therefore necessary to better understand the biological and molecular determinants of tissue regeneration and to develop new strategies to promote epithelial repair. Interestingly, a growing body of evidence indicates that many members of the large and widely expressed family of K(+) channels are involved in regulation of cell migration and proliferation, key processes of epithelial repair.

Pivotal role of the lipid Raft SK3-Orai1 complex in human cancer cell migration and bone metastases.

The SK3 channel, a potassium channel, was recently shown to control cancer cell migration, a critical step in metastasis outgrowth. Here, we report that expression of the SK3 channel was markedly associated with bone metastasis. The SK3 channel was shown to control constitutive Ca(2+) entry and cancer cell migration through an interaction with the Ca(2+) channel Orai1.

Altered SK3/KCa2.3-mediated migration in adenomatous polyposis coli (Apc) mutated mouse colon epithelial cells.

Lost of adenomatous polyposis coli gene (Apc) disturbs the migration of intestinal epithelial cells but the mechanisms have not been fully characterized. Since we have demonstrated that SK3/KCa2.3 channel promotes cancer cell migration, we hypothesized that Apc mutation may affect SK3/KCa2.

KCa2.3 channel-dependent hyperpolarization increases melanoma cell motility.

Cell migration and invasion are required for tumour cells to spread from the primary tumour bed so as to form secondary tumours at distant sites. We report evidence of an unusual expression of KCa2.3 (SK3) protein in melanoma cell lines but not in normal melanocytes.