Automated ion channel screening: patch clamping made easy

Abstract

Efficient high resolution techniques are required for screening efforts and research targeting ion channels. The conventional patch clamp technique, a high resolution but low efficiency technique, has been established for 25 years. Recent advances have opened up new possibilities for automated patch clamping. This new technology meets the need of drug developers for higher throughput and facilitates new experimental approaches in ion channel research. Specifically, Nanion's electrophysiology workstations, the Port-a-Patch and the Patchliner, have been successfully introduced as high-quality automated patch clamp platforms for industry as well as academic users. Both platforms give high quality patch clamp recordings, capable of true giga-seals and stable recordings, accessible to the user without the need for years of practical training. They also offer sophisticated experimental possibilities, such as accurate and fast ligand application, temperature control and internal solution exchange. This article describes the chip-based patch clamp technology and its usefulness in ion channel drug screening and academic research.

Molecular dynamics simulations of potassium channels

“…Such an expansion in the number of membrane proteins is due to the fact that technological advances have allowed structural biology to reach a position where the elucidation of the three-dimensional structure of relevant proteins on a large scale appears possible. At the same time high-throughput approaches are emerging [8][9][10] to characterize membrane proteins and analyze their topology, issues of significant interest for drug discovery. Unfortunately, the expression and crystallization of integral membrane proteins, such as ion channels, is still fraught with difficulties.…”

A Short Guide to Electrophysiology and Ion Channels

“…There are numerous planar-array based systems available on the market, however, the first widely available plate-based electrophysiology measurement platform was IonWorks HT, now owned by Molecular Devices, which comprises of computer-controlled fluid handling, recording electronics, and processing tools, which allows voltage clamp recordings of up to 384 individual cells per experiment (19,20). The cells are placed in a single hole on the planar chip and the system generates some 100 megaohm seal.…”

“…The system uses glass substrates for parallel patch clamp recordings from 16 wells and allows continuous recordings during ligand applications. The electrical access is achieved by rupturing the membrane of the cell underneath the aperture (20,23).…”

Drug Screening and Drug Safety Evaluation by Patch Clamp Technique

“…In 2006, Nanion attempted a higher-throughput device, the Patchliner, which supports true giga-seal recordings from up to eight cells simultaneously. It also expands the microfluidic exchange capability of both the internal and the external solutions (Farre et al, 2007). Three NPC-16 chips can be mounted on the chip loading area which means that up to 48 experiments can be preprogrammed and executed, where patch clamp measurements are possible in the whole-cell, cell-attached and perforated-patch recording configurations, and temperature controller in these two platforms supports experiments at physiological temperatures (Fig 3e).…”