Toward a comprehensive molecular model of active calcium reabsorption

The fine tuning of Ca2+ excretion in the kidney takes place in the distal n ephron, which consists of the distal convoluted tubule, connecting tubule, and initial portion of the cortical collecting duct. In these segments, Ca2 + is reabsorbed through an active transcellular pathway. The apical influx of Ca2+ into the distal renal cell is presumably the rate-limiting step in this process, and its molecular identity has remained obscure so far The re cently discovered epithelial Ca2+ channel (ECaC) exhibits tart: expected pr operties for being the gatekeeper in transcellular Ca2+ reabsorption. The c haracteristics and potential physiological role of ECaC will be discussed i n this review. Our knowledge of the mechanisms involved in the regulation o f transcellular Ca2+ transport has advanced rapidly since the development o f cell models originating from distal tubular cells. Studies using these mo dels indicate that hormones including arginine vasopressin, PGE(2), adenosi ne, ATP, and atrial natriuretic peptide should be considered as calciotropi c hormones controlling renal Ca2+ handling. Evidence is now beginning to em erge that the stimulating calciotropic hormones utilize new cAMP-independen t pathways to stimulate Ca2+ reabsorption. These new findings allow the dev elopment of a comprehensive and detailed model of the process of transcellu lar calcium transport in the kidney whereby the individual contribution of the participating transporters can now be fully appreciated.