Modulation of the human polycystin‐L channel by voltage and divalent cations

FEBS Letters

Liu, Yan¹  Zhang, Yu-Yang¹  Li, Qiang¹  Zhou, Jing²  Chen, Xing-Zhen¹  Karpinski, Edward¹  Tan, Miao¹ 

[1] Membrane Protein Research Group, Department of Physiology, University of Alberta, 729 MSB, Edmonton, AB, Canada T6G 2H7;Renal Division and Membrane Biology Program, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA

关键词: Electrophysiology;    Autosomal dominant polycystic kidney disease;    Patch-clamp;    Two-electrode voltage clamp;    Calcium;    Magnesium;    Xenopus oocyte;   

DOI  :  10.1016/S0014-5793(02)03071-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 Ca²⁺-permeable, Ca²⁺-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 Ca²⁺, K⁺ and Na⁺, PCL was highly permeable to NH₄ ⁺ and Cs⁺ with a permeability ratio NH₄ ⁺: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 Mg²⁺ 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 Mg²⁺ are modulated by membrane potential.

【 授权许可】

Unknown