Bicarbonate permeation through anion channels: its role in health and disease

Many anion channels, frequently referred as Cl^- channels, are permeable to different anions in addition to Cl^-. As the second-most abundant anion in the human body, HCO₃^- permeation via anion channels has many important physiological roles. In addition to its classical role as an intracellular pH regulator, HCO₃^- also controls the activity and stability of dissolved proteins in bodily fluids such as saliva, pancreatic juice, intestinal fluid, and airway surface liquid. Moreover, HCO₃^- permeation through these channels affects membrane potentials that are the driving forces for transmembrane transport of solutes and water in epithelia and affect neuronal excitability in nervous tissue. Consequently, aberrant HCO₃^- transport via anion channels causes a number of human diseases in respiratory, gastrointestinal, genitourinary, and neuronal systems. Notably, recent studies have shown that the HCO₃^- permeabilities of several anion channels are not fixed and can be altered by cellular stimuli, findings which may have both physiological and pathophysiological significance. In this review, we summarize recent progress in understanding the molecular mechanisms and the physiological roles of HCO₃^- permeation through anion channels. We hope that the present discussions can stimulate further research into this very important topic, which will provide the basis for human disorders associated with aberrant HCO₃^- transport.