TRPV5 and TRPV6 in Ca(2+) (re)absorption: regulating Ca(2+) entry at the gate

Many physiological functions rely on the exact maintenance of body Ca(2+) balance. Therefore, the extracellular Ca(2+) concentration is tightly regulated by the concerted actions of intestinal Ca(2+) absorption, exchange of Ca(2+) to and from bone, and renal Ca(2+) 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 Ca(2+) at large and highly variable rates. Two members of the transient receptor potential (TRP) superfamily, TRP vanilloid (TRPV)5 and TRPV6, are specialized epithelial Ca(2+) channels responsible for the critical Ca(2+) entry step in transcellular Ca(2+) (re)absorption in intestine and kidney, respectively. Because transcellular Ca(2+) transport is fine-tuned to the body's specific requirements, regulation of the transmembrane Ca(2+) 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 Ca(2+) influx through the epithelial Ca(2+) channels TRPV5 and TRPV6 in transcellular Ca(2+) (re)absorption.