Une pompe pour la sécrétion proximale de protons

Abstract

The proximal tubule of the nephron is responsible for considerable bicarbonate reabsorption. This transport is achieved indirectly through net secretion of protons. Three mechanisms are capable of H+ secretion in the tubular lumen. Amongst them, a specific H+ pump is thought to contribute to this function but the magnitude of its contribution is undefined. We have demonstrated in the dog BBM the presence of a protein capable of transporting H+ upon energization by ATP. This H+ pump resents the pharmacologic characteristics of a vacuolar H+-ATPase. We have examined the metabolic cost of H+ secretion through this mechanism in intact dog tubules in suspension. We demonstrate that this activity is a major ATP-requiring process, requiring nearly 50 % of the local ATP turnover. The activity of this pump is modulated by intracellular pH and by several other modes of regulation. Theoritical considerations on its putative implication in human diseases such as tubular acidosis type II and Fanconi syndrome are provided.