IonWorks™ HT:: A new high-throughput electrophysiology measurement platform

被引:179
作者
Schroeder, K
Neagle, B
Trezise, DJ
Worley, J
机构
[1] Essen Instruments, Ann Arbor, MI 48108 USA
[2] GlaxoSmithKline, Stevenage, Herts, England
[3] GlaxoSmithKline, Res Triangle Pk, NC USA
关键词
potassium channels; sodium channels; electrophysiology; drug screening;
D O I
10.1177/1087057102239667
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
To address the throughput restrictions of classical patch clamp electrophysiology, Essen Instruments has developed a plate-based electrophysiology measurement platform. The instrument is an integrated platform that consists of computer-controlled fluid handling, recording electronics, and processing tools capable of voltage clamp whole-cell recordings from thousands of individual cells per day. To establish a recording, the system uses a planar, multiwell substrate (a PatchPlate(TM)). The system effectively positions ` cell into a hole separating 2 fluid compartments in each well of the substrate. Voltage control and current recordings from the cell membrane are made subsequent to gaining access to the cell interior by applying a permeabilizing agent to the intracellular side. Based on the multiwell design of the PatchPlate(TM), voltage clamp recordings of up to 384 individual cells can be made in minutes and are comparable to measurements made using traditional electrophysiology techniques. An integrated pipetting system allows for up to 2 additions of modulation agents. Typical throughput, measurement fidelity, stability, and comparative pharmacology of a recombinant voltage-dependent sodium channel (hNav1.3) and a voltage-gated potassium channel (hKv1.5) exogenously expressed in CHO cells are presented. The lonWorks(TM) HT device can be used in biophysical and pharmacological profiling of ion channels in an environment compatible with high-capacity screening.
引用
收藏
页码:50 / 64
页数:15
相关论文
共 24 条
[1]   Cloning, distribution and functional analysis of the type III sodium channel from human brain [J].
Chen, YH ;
Dale, TJ ;
Romanos, MA ;
Whitaker, WRJ ;
Xie, XM ;
Clare, JJ .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2000, 12 (12) :4281-4289
[2]  
COLE KS, 1949, ARCH SCI PHYSIOL, V3, P253
[3]  
DUKES ID, 1989, AM J PHYSIOL, V257, pH1746, DOI 10.1152/ajpheart.1989.257.5.H1746
[4]  
DUKES ID, 1990, J PHARMACOL EXP THER, V254, P560
[5]  
GONOI T, 1985, J NEUROSCI, V5, P2559
[6]  
GRISSMER S, 1994, MOL PHARMACOL, V45, P1227
[7]   IMPROVED PATCH-CLAMP TECHNIQUES FOR HIGH-RESOLUTION CURRENT RECORDING FROM CELLS AND CELL-FREE MEMBRANE PATCHES [J].
HAMILL, OP ;
MARTY, A ;
NEHER, E ;
SAKMANN, B ;
SIGWORTH, FJ .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 1981, 391 (02) :85-100
[8]  
Hille B., 2001, Ion channels of excitable membranes, V3rd
[9]   THE DUAL EFFECT OF MEMBRANE POTENTIAL ON SODIUM CONDUCTANCE IN THE GIANT AXON OF LOLIGO [J].
HODGKIN, AL ;
HUXLEY, AF .
JOURNAL OF PHYSIOLOGY-LONDON, 1952, 116 (04) :497-506
[10]   A QUANTITATIVE DESCRIPTION OF MEMBRANE CURRENT AND ITS APPLICATION TO CONDUCTION AND EXCITATION IN NERVE [J].
HODGKIN, AL ;
HUXLEY, AF .
JOURNAL OF PHYSIOLOGY-LONDON, 1952, 117 (04) :500-544