Transient receptor potential channels in the kidney: calcium signaling, transport and beyond.
Multiple cationic channels with variable selectivity for Ca(2+) , K(+) and Na(+) have been identified in smooth muscle cells (SMC) as well as non-excitable cells. They control Ca(2+) store refilling and depletion, G-protein-mediated receptor activation, apoptosis and cell growth, membrane potential, intracellular pH, oxidative stress, phospholipid signaling, and other critical cell functions. A novel superfamily of divalent cation channels has been recently characterized as highly conserved heterotetramer homologues of Drosophila transient receptor potential (TRP). At least 50 members of seven major TRP channel families have been identified to date. The involvement of TRP in store-operated Ca(2+) - gating has been demonstrated in various tissues, along with intestinal and renal epithelial cell Ca(2+) and Mg(2+) transport, indicating a role in total body homeostasis of divalent cations. TRPV5-null mice display phenotypic defects including hypercalciuria and impaired bone mineral density. TRPP2 or polycystin 2 (PC2), encoded by the PKD2 gene, is an integral protein of epithelial cilia whose mutation is associated with autosomal dominant polycystic kidney disease (ADPKD). A TRPP1 (polycystin 1)-PC2 channel complex is actually implicated in the transduction of environmental signals (i.e. luminal tubular fluid flow and composition) into cellular events, such as epithelial cell growth. TRP channels can eventually play a role in the pathogenesis of arterial hypertension via direct effects on vascular smooth muscle contraction, renal blood flow, glomerular hemodynamics and the tubular handling of Ca(2+) and electrolytes.
Menè
Paolo
P
Department of Clinical Sciences, Second Medical School, University of Rome La Sapienza, Italy. Paolo.Mene@uniromal.it
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D017136:Ion Transport / Q000502:physiology; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D050051:Transient Receptor Potential Channels / Q000378:metabolism*
D050051:Transient Receptor Potential Channels; D002118:Calcium