Editing Patch clamp (section)

=== Outside-out patch ===
[[File:Outside-Out Patch Clamp.png|thumb|right|upright=1.5|Outside-out patch formation technique. In order: top-left, top-right, bottom-left, bottom-right]]
The name "outside-out" emphasizes both this technique's complementar{{shy}}ity to the inside-out technique, and the fact that it places the external rather than intracellular surface of the cell membrane on the outside of the patch of membrane, in relation to the patch electrode.<ref name="Hamill, et al - Outside-out" />

The formation of an outside-out patch begins with a whole-cell recording configuration. After the whole-cell configuration is formed, the electrode is slowly withdrawn from the cell, allowing a bulb of membrane to [[bleb (cell biology)|bleb]] out from the cell. When the electrode is pulled far enough away, this bleb will detach from the cell and reform as a convex membrane on the end of the electrode (like a ball open at the electrode tip), with the original outside of the membrane facing outward from the electrode.<ref name="Hamill, et al - Outside-out"/> As the image at the right shows, this means that the fluid inside the pipette will be simulating the intracellular fluid, while a researcher is free to move the pipette and the bleb with its channels to another bath of solution. While multiple channels can exist in a bleb of membrane, single channel recordings are also possible in this conformation if the bleb of detached membrane is small and only contains one channel.<ref name="Howe, Cull-Candy, & Colquhoun - Outside-out">{{cite journal|last1=Howe|first1=JR|last2=Cull-Candy|first2=SG|last3=Colquhoun|first3=D|title=Currents through single glutamate receptor channels in outside-out patches from rat cerebellar granule cells|journal=Journal of Physiology|date=Jan 1991|volume=432|issue=1|pages=143–202|pmid=1715916|pmc=1181322|doi=10.1113/jphysiol.1991.sp018381}}</ref>

Outside-out patching gives the experimenter the opportunity to examine the properties of an ion channel when it is isolated from the cell and exposed successively to different solutions on the [[extracellular]] surface of the membrane. The experimenter can perfuse the same patch with a variety of solutions in a relatively short amount of time, and if the channel is activated by a [[neurotransmitter]] or drug from the extracellular face, a [[Dose-response relationship|dose-response]] curve can then be obtained.<ref name="von Beckerath, et al - Outside-out">{{cite journal|last1=von Beckerath|first1=N|last2=Adelsberger|first2=H|last3=Parzefall|first3=F|last4=Franke|first4=C|last5=Dudel|first5=J|title=GABAergic inhibition of crayfish deep extensor abdominal muscle exhibits a steep dose-response relationship and a high degree of cooperativity|journal=European Journal of Physiology|date=Apr 1995|volume=429|issue=6|pages=781–788|pmid=7541524|doi=10.1007/bf00374801|s2cid=7824699}}</ref> This ability to measure current through exactly the same piece of membrane in different solutions is the distinct advantage of the outside-out patch relative to the cell-attached method. On the other hand, it is more difficult to accomplish. The longer formation process involves more steps that could fail and results in a lower frequency of usable patches.