Editing Patch clamp (section)

=== Perforated patch ===
[[File:Perforated Patch Clamp.png|thumb|right|Perforated patch technique]]
This variation of the patch clamp method is very similar to the whole-cell configuration. The main difference lies in the fact that when the experimenter forms the gigaohm seal, suction is not used to rupture the patch membrane. Instead, the electrode solution contains small amounts of an antifungal or [[antibiotic]] agent, such as [[amphothericin-B]], [[nystatin]], or [[gramicidin]], which diffuses into the membrane patch and forms small pores in the membrane, providing electrical access to the cell interior.<ref name=Linley /> When comparing the whole-cell and perforated patch methods, one can think of the whole-cell patch as an open door, in which there is complete exchange between molecules in the pipette solution and the cytoplasm. The perforated patch can be likened to a screen door that only allows the exchange of certain molecules from the pipette solution to the cytoplasm of the cell.

Advantages of the perforated patch method, relative to whole-cell recordings, include the properties of the antibiotic pores, that allow equilibration only of small monovalent ions between the patch pipette and the cytosol, but not of larger molecules that cannot permeate through the pores. This property maintains endogenous levels of 
divalent ions such as Ca<sup>2+</sup> and signaling molecules such as [[Cyclic adenosine monophosphate|cAMP]]. Consequently, one can have recordings of the entire cell, as in whole-cell patch clamping, while retaining most intracellular signaling mechanisms, as in cell-attached recordings. As a result, there is reduced current rundown, and stable perforated patch recordings can last longer than one hour.<ref name=Linley>{{cite book|last1=Linley|first1=John|title=Ion Channels|editor1-last=Gamper|editor1-first=Nikita|chapter=Perforated Whole-Cell Patch-Clamp Recording|date=2013|publisher=Humana Press|isbn=978-1-62703-351-0|pages=149–157|edition=Second|series=Methods in Molecular Biology|volume=998|doi=10.1007/978-1-62703-351-0_11|pmid=23529427}}</ref> Disadvantages include a higher access resistance, relative to whole-cell, due to the partial membrane occupying the tip of the electrode. This may decrease current resolution and increase recording noise. It can also take a significant amount of time for the antibiotic to perforate the membrane (about 15 minutes for amphothericin-B, and even longer for gramicidin and nystatin). The membrane under the electrode tip is weakened by the perforations formed by the antibiotic and can rupture. If the patch ruptures, the recording is then in whole-cell mode, with antibiotic contaminating the inside of the cell.<ref name=Linley />