Chloride ions in health and disease

Abstract

Abstract Chloride is a key anion involved in cellular physiology by regulating its homeostasis and rheostatic processes. Changes in cellular Cl− concentration result in differential regulation of cellular functions such as transcription and translation, post-translation modifications, cell cycle and proliferation, cell volume, and pH levels. In intracellular compartments, Cl− modulates the function of lysosomes, mitochondria, endosomes, phagosomes, the nucleus, and the endoplasmic reticulum. In extracellular fluid (ECF), Cl− is present in blood/plasma and interstitial fluid compartments. A reduction in Cl− levels in ECF can result in cell volume contraction. Cl− is the key physiological anion and is a principal compensatory ion for the movement of the major cations such as Na+, K+, and Ca2+. Over the past 25 years, we have increased our understanding of cellular signaling mediated by Cl−, which has helped in understanding the molecular and metabolic changes observed in pathologies with altered Cl− levels. Here, we review the concentration of Cl− in various organs and cellular compartments, ion channels responsible for its transportation, and recent information on its physiological roles.