Influence of conductance changes on patch clamp capacitance measurements using a lock-in amplifier and limitations of the phase tracking technique

Biophysical Journal
K DebusM Lindau

Abstract

We characterized the influence of conductance changes on whole-cell patch clamp capacitance measurements with a lock-in amplifier and the limitations of the phase-tracking method by numerical computer simulations, error formulas, and experimental tests. At correct phase setting, the artifacts in the capacitance measurement due to activation of linear conductances are small. The cross talk into the capacitance trace is well approximately by the second-order term in the Taylor expansion of the admittance. In the case of nonlinear current-voltage relationships, the measured conductance corresponds to the slope conductance in the range of the sine wave amplitude, and the cross talk into the capacitance trace corresponds to the second-order effect of the slope conductance. The finite gating kinetics of voltage-dependent channels generate phase-shifted currents. These lead to major artifacts in the capacitance measurements when the angular frequency of the sine wave is close to the kinetic rate constant of the channel. However, when the channel kinetics are sufficiently slow, or sufficiently fast, the cross talk is still close to the second-order effect of the measured conductance. The effects of activation of voltage-dependent curre...Continue Reading

Citations

Jan 28, 2005·Journal of the Association for Research in Otolaryngology : JARO·Maria A SpassovaThomas D Parsons
Jun 21, 2006·Annals of Biomedical Engineering·Pavel Novák, Ivan Zahradník
Aug 2, 2001·The Journal of General Physiology·P ChenK D Gillis
Jan 30, 2004·Journal of Neurophysiology·Marc D EisenThomas D Parsons
May 23, 2006·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·Brenda FarrellWilliam E Brownell

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