“Clip Detecting” with series resistance compensation using an automated patch clamp system

著者: Lars Damgaard Løjkner, Chris Gibbs, Jesper Gerved, Jens Henneke, Jonatan Kutchinsky, Rasmus B Jacobsen, Morten Sunesen

Sodium ion channels are some of the fastest ion channels. With a high current and fast activation, it is very difficult for conventional amplifiers to correctly clamp these signals. The main challenge in providing a perfect clamp is the error introduced by the series resistance (Rs), which will introduce a voltage drop as the current increases rapidly (Sigworth 1983). This leads to delays in the signal and incorrect estimation of the current magnitude. In order to correctly compensate Rs fast enough, one will have to compromise on another cell parameter; cell capacitance (Cs) (Sherman 1999). In the QPatch system, it is possible to conduct experiments without direct Cs compensation, but still measure Cs for later use.

When compensating completely for Rs, oscillations may occur and this is mainly due to incorrect cell parameter estimations or that the cell simply changes slightly. Oscillations can often lead to reduction in the seal resistance and terminate the whole-cell configuration. In the QPatch system, critical current oscillations are detected and the Rs feedback loop is disconnected for the remaining of the sweep until new parameter estimations can be made.