s TRP Channels: Emerging Links Between Ca2+, Kidney and Hypertension

Cationic channels with variable selectivity for Ca2+, K+, and Na+ are ubiquitous in non-excitable tissues as well as contractile cardiac cells and vascular smooth muscle (VSMC). They are involved in multiple cell functions, including contraction and proliferation of VSMC, key to the regulation of vascular tone and blood pressure. A large superfamily includes at least 28 highly conserved heterotetramer homologues of Drosophila TRP (transient receptor potential) channels. Direct evidence exists for TRPC, TRPV, TRPP gating ion entry in vascular cells, as well as in epithelial cells of kidney and intestine, thus controlling homeostasis and external balance of divalent cations. Mice deficient in TRPV5 display phenotypic defects resembling human idiopathic hypercalciuria and impaired bone mineral density. Polycystin 2, encoded by the PKD2 gene, is an epithelial transmembrane TRPP2 protein, whose mutation is associated with autosomal dominant polycystic kidney disease (ADPKD). TRP ion channels may therefore play a role in the pathogenesis of systemic arterial hypertension, pulmonary hypertension, as well as hypertension complicating renal disease via effects on vascular tone and/or on the electrolyte composition of body fluids.