This Article Full Text (PDF) All Versions of this Article: 1087057106288050v1 11/5/488    most recent References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (30) Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Finkel, A. Articles by Costantin, J. Search for Related Content PubMed PubMed Citation Articles by Finkel, A. Articles by Costantin, J. Social Bookmarking                         What's this?

Population Patch Clamp Improves Data Consistency and Success Rates in the Measurement of Ionic Currents

Molecular Devices Corporation, Union City, California.

Andrew Wittel

Molecular Devices Corporation, Union City, California; Amgen Inc., Thousand Oaks, California.

Naibo Yang

Shawn Handran

Jan Hughes

Molecular Devices Corporation, Union City, California.

James Costantin

Molecular Devices Corporation, 3280 Whipple Road, Union City, CA 94587 james.costantin{at}moldev.com

Present whole-cell patch-clamp methodology has only moderate consistency and throughput, rendering impractical functional measurements on large numbers of ion channel ligands or on large numbers of unknown or mutant channel genes. In the population patch clamp (PPC) described herein, a single voltage-clamp amplifier sums the whole-cell currents from multiple cells at once, each sealed to a separate aperture in a planar substrate well. The resulting ensemble currents are more consistent from well to well, and the success rate for each recording attempt is >95%. The PPC was implemented by modifying the PatchPlate substrate and amplifiers in the IonWorks patch-clamp instrument. The increased data consistency and likelihood of a successful recording in each well, combined with 384-well measurements in parallel, allow the direct electrophysiological recording of thousands of ensemble ionic currents per day. Therapeutic groups in drug discovery programs require this order of throughput to screen directed compound libraries against ion channel targets. The potential for studying the function of large numbers of ion channel mutants may be realized with the technique. The procedure incorporates subtraction methods that correct for expected distortions and also reliably produces data that agree with previous patch-clamp studies.

Key Words: ion channel • electrophysiology • patch clamp • planar patch • population patch clamp

This version was published on August 1, 2006

Journal of Biomolecular Screening, Vol. 11, No. 5, 488-496 (2006)
DOI: 10.1177/1087057106288050


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				E. C. Hollands, T. J. Dale, A. W. Baxter, H. J. Meadows, A. J. Powell, J. J. Clare, and D. J. Trezise Population Patch-Clamp Electrophysiology Analysis of Recombinant GABAA {alpha}1{beta}3{gamma}2 Channels Expressed in HEK-293 Cells J Biomol Screen, August 1, 2009; 14(7): 769 - 780. [Abstract] [PDF]

				V. H. John, T. J. Dale, E. C. Hollands, M. X. Chen, L. Partington, D. L. Downie, H. J. Meadows, and D. J. Trezise Novel 384-Well Population Patch Clamp Electrophysiology Assays for Ca2+-Activated K+ Channels J Biomol Screen, February 1, 2007; 12(1): 50 - 60. [Abstract] [PDF]