Patch Configurations
A summary of the most common techniques used to measure the electrical properties of cell membranes

Patch-clamp technique uses a glass pipette filled with a conductive liquid to measure voltage inside the neuron. The pipette is lowered onto the surface of a cell until it forms a seal with the cell membrane (called a cell-attached or on-cell configuration), as seen in A. Although cell-attached configuration allows some measurements to be performed, more advanced electrical measurements can be performed by breaking the small patch of cell membrane separating the patch pipette internal solution from the cellular cytoplasm. A small burst of negative pressure (suction) ruptures this patch, turning a cell-attached configuration to a whole-cell configuration, as seen in C. Although it is possible to pull part of the cell membrane away from the cell (as in B and D) to perform smaller-scale studies (i.e., single channel recordings), these techniques are best performed using specialized electrical and mechanical equipment which is not discussed by this document.

Comparison of different cell modes: (A) When sealed, cells are in cell-attached / on-cell mode. A patch could be ripped-off the cell to study ion channels in a small piece of membrane (B), but usually we proceed with suction to break into cell and establish whole-cell mode (C). Pulling away from the cell at this point could result in an outside-out patch (D).

🤓 Nerd Alert: consider the role or Ra in A and C. In C, a low Ra is indication of a good quality whole-cell configuration. When an experiment fails because Ra rapidly rises, it can be because the pipette began pulling away from the cell and its membrane is starting to occlude the tip of the pipette (D). While we don’t intend to do so, failed experiments are often the result of creating outside-out patches.