Zinc-permeable ion channels: effects on intracellular zinc dynamics and potential physiological/pathophysiological...

Zinc (Zn(2+)) is one of the most important trace metals in the body. It is necessary for the normal function of a large number of protein s including enzymes and transcription factors. While extracellular fluid may contain up to micromolar Zn(2+), intracellular Zn(2+) concentration is generally maintained at a subnanomolar level; this steep gradient across the cell membrane is primarily attributable to Zn(2+) extrusion by Zn(2+) transporting systems. Interestingly, systematic investigation has revealed that activities, previously believed to be dependent on calcium (Ca(2+)), may be partially mediated by Zn(2+). This is also supported by new findings that some Ca(2+)-permeable channels such as voltage-dependent calcium channels (VDCCs), N-methyl-D-aspartate receptors (NMDA), and amino-3- hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPA-Rs) are also permeable to Zn(2+). Thus, the importance of Zn(2+) in physiological and pathophysiological processes is now more widely appreciated. In this review, we describe Zn(2+)- permeable membrane molecules, especially Zn(2+)-permeable ion channels, in intracellular Zn(2+)dynamics and Zn(2+) mediated physiology/pathophysiology.