Inner mitochondrial maxi-K ⁺ channels in neonatal renal tubular cells: Novel therapeutic targets to control apoptosis

In developing kidneys, the total cell population is partly regulated by apoptosis. Despite our understanding of the molecular involvement in the regulatory pathway of apoptosis, we know little about the physiological involvement. Cardiomyocytes express large conductance voltage- and Ca ²⁺-activated K ⁺ (maxi-K ⁺) channels in their inner mitochondrial membranes. Triggering the mitochondrial K ⁺ influx necessary to inhibit apoptosis, the channels play cytoprotective roles during ischemic injury. Since proximal tubular cells in neonatal kidneys are physiologically under hypoxic stress, and since the channel activity is stimulated by hypoxia, those cells would share the same regulatory mechanism of apoptosis with ischemic cardiomyocytes. Therefore, we hypothesize here that the proximal tubular cells in neonatal kidneys would also express the maxi-K ⁺ channels in their inner mitochondrial membranes, and that the channels would play regulatory roles in apoptosis. Our hypothesis is unique because it sheds light for the first time on a physiological mechanism that involves the mitochondrial membranes in developing kidneys. It is also important because the idea could have novel therapeutic implications for kidney diseases that are associated with apoptosis.