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Modulation of the human polycystin‐L channel by voltage and divalent cations
Author(s) -
Liu Yan,
Li Qiang,
Tan Miao,
Zhang Yu-Yang,
Karpinski Edward,
Zhou Jing,
Chen Xing-Zhen
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)03071-5
Subject(s) - divalent , depolarization , chemistry , xenopus , biophysics , conductance , patch clamp , membrane potential , voltage clamp , biochemistry , biology , receptor , gene , organic chemistry , mathematics , combinatorics
Polycystin‐L (PCL) is highly homologous in sequence and membrane topology to polycystin‐2, the product of the second gene responsible for autosomal dominant polycystic kidney disease (ADPKD). PCL and polycystin‐2 were recently shown to be Ca 2+ ‐permeable, Ca 2+ ‐activated cation channels. Further characterization of polycystins will help in the understanding of cystogenesis and pathogenesis of ADPKD. In the present study, we expressed human PCL in Xenopus oocytes and studied its function utilizing patch‐clamp and two‐electrode voltage clamp techniques. In addition to its permeability to Ca 2+ , K + and Na + , PCL was highly permeable to NH 4 + and Cs + with a permeability ratio NH 4 + :Cs + :Na + of 2.2:1.02:1. Voltage modulation of channel properties was studied using cell‐attached (C‐A) and excised inside‐out (I‐O) patches. In the C‐A mode, the open probability (NP o ) of PCL at negative potentials (NP o =0.22) was higher than at positive potentials (NP o =0.05). The mean open time averaged 31.6 ms at negative potentials, and 6.2 ms at positive potentials; single‐channel activity exhibited bursts with a mean interburst time of 178 ms. Using I‐O patches under symmetrical ionic conditions, single‐channel inward conductance was significantly larger than outward conductance, indicating a slight inward rectification. External Mg 2+ inhibited the PCL channel currents. The inhibitory effect was voltage‐dependent and substantially reduced by depolarization. The time course of inactivation depended on external calcium concentration but was independent of voltage and peak current. This study shows that although PCL is not a voltage‐gated channel, its channel activity and inhibition by Mg 2+ are modulated by membrane potential.