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 bodys 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.