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

Polycystic kidney diseases are genetic disorders in which the renal parench yma is progressively replaced by fluid-filled cysts(1). Two members of the polycystin family (polycystin-1 and -2) are mutated in autosomal dominant p olycystic kidney disease (ADPKD)(2-5), and polycystin-L is deleted in mice with renal and retinal defects(6), Polycystins are membrane proteins that s hare significant sequence homology(6,7), especially polycystin-2 and -L (50 % identity and 71% similarity). The functions of the polycystins remain unk nown. Here we show that polycystin-L is a calcium-modulated nonselective ca tion channel that is permeable to sodium, potassium and calcium ions. Patch -clamp experiments revealed single-channel activity with a unitary conducta nce of 137 pS. Channel activity was substantially increased when either the extracellular or intracellular calcium-ion concentration was raised, indic ating that polycystin-L may act as a transducer of calcium-mediated signall ing in vivo. Its large single-channel conductance and regulation by calcium ions distinguish it from other structurally related cation channels.