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

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

Research output: Contribution to journalArticlepeer-review

187 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)383-386
Number of pages4
JournalNature
Volume401
Issue number6751
DOIs
StatePublished - Sep 23 1999

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