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Originally published as Biophys J. BioFAST on October 29, 2004.
doi:10.1529/biophysj.104.049866
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Biophysical Journal 88:739-750 (2005)
© 2005 The Biophysical Society

The Interpretation of Current-Clamp Recordings in the Cell-Attached Patch-Clamp Configuration

M. J. Mason, A. K. Simpson, M. P. Mahaut-Smith and H. P. C. Robinson

Department of Physiology, University of Cambridge, United Kingdom

Correspondence: Address reprint requests to Dr. Michael J. Mason, Dept. of Physiology, University of Cambridge, Downing St., Cambridge CB2 3EG, UK. Tel.: 44-1223-333899; E-mail: mjm39{at}cam.ac.uk.

In these experiments we have investigated the feasibility and accuracy of recording steady-state and dynamic changes in transmembrane potential noninvasively across an intact cell-attached patch using the current-clamp mode of a conventional patch-clamp amplifier. Using an equivalent circuit mimicking simultaneous whole-cell voltage-clamp and cell-attached current-clamp recordings we have defined both mathematically and experimentally the relationship between the membrane patch resistance, the seal resistance, and the fraction of the whole-cell potential recorded across an intact membrane patch. This analysis revealed a steep increase in the accuracy of recording of steady-state membrane potential as the seal/membrane ratio increases from 0. The recording accuracy approaches 100% as the seal/membrane ratio approaches infinity. Membrane potential measurements across intact cell-attached patches in rat basophilic leukemia cells and rat megakaryocytes revealed a surprisingly high degree of accuracy and demonstrated the ability of this noninvasive technique to follow dynamic changes in potential in nonexcitable cells.




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