Role of ion channels in salt secretion by atlantic salmon gills during acclimation to seawater

Smoltification, also called parr-smolt transformation, is a complex developmental process that consists of a number of independent, but coordinated changes, in the biochemistry, physiology, morphology and behavior of juvenile salmon in their transition from freshwater to seawater life. A key component of smoltification is represented by the physiological adaptations that enable smolts to thrive in hyperosmotic environments. Instrumental to this process is the ability of smolt gills to gradually become capable of actively secreting salt through specialized cells known as mitochondria-rich (MR) cells, ionocytes or chloride cells. NaCl secretion by teleost gills is therefore accomplished via the secondary active transport of Cl⁻ and the passive transport of Na⁺. The driving force for active transport is provided by Na⁺/K⁺ ATPase, which maintains low intracellular Na⁺ and high intracellular K⁺ concentrations. However, this NaCl secretion mechanism needs at least two different ion channels: A CFTR type chloride channel for the passive exit of Cl⁻ and a potassium channel to recycle extracellular K⁺, which is a thermodynamic prerequisite to work under conditions imposed by high extracellular salinity in seawater. The characteristics of K⁺ channels required for NaCl secretion from MR cells into seawater are still unknown for Salmo salar and only recently have begun to be studied in other teleosts.Sociedad Argentina de Fisiologí

Ion Channel Drugs Suppress Cancer Phenotype in NG108-15 and U87 Cells: Toward Novel Electroceuticals for Glioblastoma

Glioblastoma is a lethal brain cancer that commonly recurs after tumor resection and chemotherapy treatment. Depolarized resting membrane potentials and an acidic intertumoral extracellular pH have been associated with a proliferative state and drug resistance, suggesting that forced hyperpolarization and disruption of proton pumps in the plasma membrane could be a successful strategy for targeting glioblastoma overgrowth. We screened 47 compounds and compound combinations, most of which were ion-modulating, at different concentrations in the NG108-15 rodent neuroblastoma/glioma cell line. A subset of these were tested in the U87 human glioblastoma cell line. A FUCCI cell cycle reporter was stably integrated into both cell lines to monitor proliferation and cell cycle response. Immunocytochemistry, electrophysiology, and a panel of physiological dyes reporting voltage, calcium, and pH were used to characterize responses. The most effective treatments on proliferation in U87 cells were combinations of NS1643 and pantoprazole; retigabine and pantoprazole; and pantoprazole or NS1643 with temozolomide. Marker analysis and physiological dye signatures suggest that exposure to bioelectric drugs significantly reduces proliferation, makes the cells senescent, and promotes differentiation. These results, along with the observed low toxicity in human neurons, show the high efficacy of electroceuticals utilizing combinations of repurposed FDA approved drugs