MODALITIES OF DISTORTION OF PHYSIOLOGICAL VOLTAGE SIGNALS BY PATCH-CLAMP AMPLIFIERS - A MODELING STUDY

An extensive evaluation of the possible alterations affecting physiolo gical voltage signals recorded with patch-clamp amplifiers (PCAs) work ing in the current-clamp (CC) mode was carried out by following a mode ling approach. The PCA output voltage and current signals obtained dur ing CC recordings performed under simplified experimental conditions w ere exploited to determine the equations describing the generation of error currents and voltage distortions by PCAs. The functions thus obt ained were used to construct models of PCAs working in the CC mode, wh ich were coupled to numerical simulations of neuronal bioelectrical be havior; this allowed us to evaluate the effects of the same PCAs on di fferent physiological membrane-voltage events. The models revealed tha t rapid signals such as fast action potentials are preferentially affe cted, whereas slower events, such as low-threshold spikes, are less al tered. Prominent effects of model PCAs on fast action potentials were alterations of their amplitude, duration, depolarization and repolariz ation speeds, and, most notably, the generation of spurious afterhyper polarizations. Processes like regular firing and burst firing could al so be altered, under particular conditions, by the model PCAs. When a cell consisting of more than one single intracellular compartment was considered, the model PCAs distorted fast equalization transients. Fur thermore, the effects of different experimental and cellular parameter s (series resistance, cell capacitance, temperature) on PCA-generated artifacts were analyzed. Finally, the simulations indicated that no of f-line correction based on manipulations of the error-current signals returned by the PCAs can be successfully performed in the attempt to r ecover unperturbed voltage signals, because of alterations of the over all current flowing through the cell-PCA system.