TRPV5 and TRPV6 in Ca2+ (re)absorption:: regulating Ca2+ entry at the gate

Many physiological functions rely on the exact maintenance of body Ca2+ balance. Therefore, the extracellular Ca2+ concentration is tightly regulated by the concerted actions of intestinal Ca2+ absorption, exchange of Ca2+ to and from bone, and renal Ca2+ reabsorption. Renal distal convoluted and connecting tubular cells as well as duodenal epithelial cells are unique in their ability to mediate transcellular ( re) absorption of Ca2+ at large and highly variable rates. Two members of the transient receptor potential (TRP) superfamily, TRP vanilloid (TRPV) 5 and TRPV6, are specialized epithelial Ca2+ channels responsible for the critical Ca2+ entry step in transcellular Ca2+ ( re) absorption in intestine and kidney, respectively. Because transcellular Ca2+ transport is fine-tuned to the body's specific requirements, regulation of the transmembrane Ca2+ flux through TRPV5/6 is of particular importance and has, therefore, to be conspicuously controlled. We present an overview of the current knowledge and recent advances concerning the coordinated regulation of Ca2+ influx through the epithelial Ca2+ channels TRPV5 and TRPV6 in transcellular Ca2+ ( re) absorption.