Polycystin-L is a calcium-regulated cation channel permeable to calcium ions

• DOI: 10.1038/43907
• Publication Date: 2006-07-21T14:52:06Z
• Authors: Xing-Zhen Chen; Peter M. Vassilev; Nuria Basora; Ji-Bin Peng; Hideki Nomura; Yoav Segal; Edward M. Brown; Stephen T. Reeders; Matthias A. Hediger; Jing Zhou
• Keywords: N-type calcium channel; BK channel; R-type calcium channel; Calcium Signaling; Calcium-activated potassium channel; Calcium in biology

Polycystic kidney diseases are genetic disorders in which the renal parenchyma is progressively replaced by fluid-filled cysts. Two members of the polycystin family (polycystin-1 and -2) are mutated in autosomal dominant polycystic kidney disease (ADPKD), and polycystin-L is deleted in mice with renal and retinal defects. Polycystins are membrane proteins that share significant sequence homology, especially polycystin-2 and -L (50% identity and 71% similarity). The functions of the polycystins remain unknown. Here we show that polycystin-L is a calcium-modulated nonselective cation channel that is permeable to sodium, potassium and calcium ions. Patch-clamp experiments revealed single-channel activity with a unitary conductance of 137 pS. Channel activity was substantially increased when either the extracellular or intracellular calcium-ion concentration was raised, indicating that polycystin-L may act as a transducer of calcium-mediated signalling in vivo. Its large single-channel conductance and regulation by calcium ions distinguish it from other structurally related cation channels.