Bisphosphonates (BPs) reduce bone pain and fractures by balancing the osteoblast/osteoclast ratio. The behavior of ion channels in the presence of BPs is not known. To investigate this, the effect of zoledronic acid BP (ZOL) (3 × 10⁻⁸ to 5 × 10⁻⁴ M) treatment, on ion channels, cell proliferation, and mineralization, has been investigated on preosteoclast-like cells, RAW264.7, preosteoblast-like cells MC3T3-E1, and rat/mouse native bone marrow-derived osteoblasts. In whole-cell patch clamp on cell line- and bone marrow-derived osteoblasts, ZOL potentiated outward currents. On RAW264.7, ZOL (10⁻⁴ M)-evoked current was reduced by the Kv channel blocker tetraethylammonium hydrochloride (TEA), but not by the selective TRPV1-channel antagonist capsazepine. On MC3T3-E1 cells and bone marrow-derived osteoblasts, ZOL-evoked current (5 × 10⁻⁸ to 10⁻⁴ M) was reduced by capsazepine, whereas the selective TRPV1-channel agonist capsaicin potentiated the control current. In the cell proliferation assay, 72 h incubation of RAW264.7 and MC3T3-E1 cells with ZOL reduced proliferation, with IC₅₀ values of 2.62 × 10⁻⁷ M and 2.02 × 10⁻⁵ M, respectively. Mineralization of MC3T3-E1 cells and bone marrow-derived osteoblasts was observed in the presence of capsaicin and ZOL (5 × 10⁻⁸–10⁻⁷ M); ZOL effects were antagonized by capsazepine. In summary, the ZOL-induced activation of TRPV1 channel mediates the mineralization of osteoblasts and counterbalances the antiproliferative effects, increasing the IC₅₀. This mechanism is not operative in osteoclasts lacking the TRPV1 channel.

Hydrogen sulfide (H₂S) is a critical gasotransmitter that plays a dual role in physiological and pathological processes, particularly in the gastrointestinal tract. While physiological levels of H₂S exert cytoprotective effects, excessive concentrations can lead to toxicity, oxidative stress, and inflammation. The aim of this study was to investigate the dose-dependent effects of exogenous H₂S on mitochondrial functions and biogenesis in intestinal epithelial cells under non-stressed conditions. Using a Caco-2 monolayer model, we evaluated the impact of sodium hydrosulfide (NaHS) at concentrations ranging from 1 × 10⁻⁷ M to 5 × 10⁻³ M on mitochondrial metabolism, redox balance, antioxidant defense, inflammatory responses, autophagy/mitophagy, and apoptosis. Our results demonstrated a biphasic response: low-to-moderate H₂S concentrations (1 × 10⁻⁷ M–1.5 × 10⁻³ M) enhance mitochondrial biogenesis through PGC-1α activation, upregulating TFAM and COX-4 expression, and increasing the mtDNA copy number. In contrast, higher concentrations (2 × 10⁻³–5 × 10⁻³ M) impair mitochondrial function, induce oxidative stress, and promote apoptosis. These effects are associated with elevated reactive oxygen species (ROS) production, dysregulation of antioxidant enzymes, and COX-2-mediated inflammation. H₂S-induced autophagy/mitophagy is a protective mechanism at intermediate concentrations but fails to mitigate mitochondrial damage at toxic levels. This study underscores the delicate balance between the cytoprotective and cytotoxic effects of exogenous H₂S in intestinal cells, helping to develop new therapeutic approaches for gastrointestinal disorders.

The ATP-sensitive K+-channels (KATP) are distributed in the tissues coupling metabolism with K+ ions efflux. KATP subunits are encoded by KCNJ8 (Kir6.1), KCNJ11 (Kir6.2), ABCC8 (SUR1) and ABCC9 (SUR2) genes, alternative RNA splicing give rise to SUR variants that confer distinct physiological properties on the channel. An high expression/activity of the sarco-KATP channel is observed in various rat fast-twitch muscles, characterized by elevated muscle strength, while a low expression/activity is observed in the slow-twitch muscles characterized by reduced strength and frailty. Down-regulation of the KATP subunits of fast-twitch fibres is found in conditions characterized by weakness and frailty. KCNJ11 gene knockout mice have reduced glycogen, lean phenotype, lower body fat, and weakness. KATP channel is also a sensor of muscle atrophy. The KCNJ11 gene is located on BTA15, close to a QTL for meat tenderness, it has also a role in glycogen storage, a key mechanism of the postmortem transformation of muscle into meat. The role of KCNJ11 gene in muscle function may underlie an effect of KCNJ11 genotypes on meat tenderness, as recently reported. The fiber phenotype and genotype are important in livestock production science. Quantitative traits including meat production and quality are influenced both by environment and genes. Molecular markers can play an important role in the genetic improvement of animals through breeding strategies. Many factors influence the muscle Warner-Bratzler shear force including breed, age, feeding, the biochemical and functional parameters. The role of KCNJ11gene and related genes on muscle tenderness will be discussed in the present review.

The effects of Ca²⁺-activated K⁺ (BK) channel modulation by Paxilline (PAX) (10⁻⁷–10⁻⁴ M), Iberiotoxin (IbTX) (0.1–1 × 10⁻⁶ M) and Resveratrol (RESV) (1–2 × 10⁻⁴ M) on cell cycle and proliferation, AKT1p^Ser473 phosphorylation, cell diameter, and BK currents were investigated in SH-SY5Y cells using Operetta-high-content-Imaging-System, ELISA-assay, impedentiometric counting method and patch-clamp technique, respectively. IbTX (4 × 10⁻⁷ M), PAX (5 × 10⁻⁵ M) and RESV (10⁻⁴ M) caused a maximal decrease of the outward K⁺ current at +30 mV (Vm) of −38.3 ± 10%, −31.9 ± 9% and −43 ± 8%, respectively, which was not reversible following washout and cell depolarization. After 6h of incubation, the drugs concentration dependently reduced proliferation. A maximal reduction of cell proliferation, respectively of −60 ± 8% for RESV (2 × 10⁻⁴ M) (IC50 = 1.50 × 10⁻⁴ M), −65 ± 6% for IbTX (10⁻⁶ M) (IC50 = 5 × 10⁻⁷ M), −97 ± 6% for PAX (1 × 10⁻⁴ M) (IC50 = 1.06 × 10⁻⁵ M) and AKT1p^ser473 dephosphorylation was observed. PAX induced a G1/G2 accumulation and contraction of the S-phase, reducing the nuclear area and cell diameter. IbTX induced G1 contraction and G2 accumulation reducing diameter. RESV induced G2 accumulation and S contraction reducing diameter. These drugs share common actions leading to a block of the surface membrane BK channels with cell depolarization and calcium influx, AKT1p^ser473 dephosphorylation by calcium-dependent phosphatase, accumulation in the G2 phase, and a reduction of diameter and proliferation. In addition, the PAX action against nuclear membrane BK channels potentiates its antiproliferative effects with early apoptosis.