Editing Patch clamp (section)

=== Loose patch ===
[[File:Loose Patch Clamp.png|thumb|right|Loose patch clamp technique]]
A loose patch clamp is different from the other techniques discussed here in that it employs a loose seal (low electrical resistance) rather than the tight gigaseal used in the conventional technique. This technique was used as early as the year 1961, as described in a paper by Strickholm on the impedance of a muscle cell's surface,<ref name="Strickholm - loose patch">{{cite journal|last1=Strickholm|first1=A|title=Impedance of a Small Electrically Isolated Area of the Muscle Cell Surface|journal=Journal of General Physiology|date=1 Jul 1961|volume=44|issue=6|pages=1073–88|pmid=19873540|pmc=2195146|doi=10.1085/jgp.44.6.1073}}</ref> but received little attention until being brought up again and given a name by Almers, Stanfield, and Stühmer in 1982,<ref name="Almers, Stanfield, & Stühmer - loose patch" /> after patch clamp had been established as a major tool of electrophysiology.

To achieve a loose patch clamp on a cell membrane, the pipette is moved slowly towards the cell, until the electrical resistance of the contact between the cell and the pipette increases to a few times greater resistance than that of the electrode alone. The closer the pipette gets to the membrane, the greater the resistance of the pipette tip becomes, but if too close a seal is formed, and it could become difficult to remove the pipette without damaging the cell. For the loose patch technique, the pipette does not get close enough to the membrane to form a gigaseal or a permanent connection, nor to pierce the cell membrane.<ref name="Lupa & Caldwell - Loose patch" /> The cell membrane stays intact, and the lack of a tight seal creates a small gap through which ions can pass outside the cell without entering the pipette.

A significant advantage of the loose seal is that the pipette that is used can be repeatedly removed from the membrane after recording, and the membrane will remain intact. This allows repeated measurements in a variety of locations on the same cell without destroying the integrity of the membrane. This flexibility has been especially useful to researchers for studying muscle cells as they contract under real physiological conditions, obtaining recordings quickly, and doing so without resorting to drastic measures to stop the muscle fibers from contracting.<ref name="Almers, Stanfield, & Stühmer - loose patch">{{cite journal |vauthors=Almers W, Stanfield PR, Stühmer W |title=Lateral distribution of sodium and potassium channels in frog skeletal muscle: measurements with a patch clamp method |journal=Journal of Physiology |year=1983 |volume=336 |issue=10 |pages=261–284 |pmc=1198969 |pmid=6308223 |doi=10.1113/jphysiol.1983.sp014580 }}</ref> A major disadvantage is that the resistance between the pipette and the membrane is greatly reduced, allowing current to leak through the seal, and significantly reducing the resolution of small currents. This leakage can be partially corrected for, however, which offers the opportunity to compare and contrast recordings made from different areas on the cell of interest. Given this, it has been estimated that the loose patch technique can resolve currents smaller than 1 mA/cm<sup>2</sup>.<ref name="Lupa & Caldwell - Loose patch">{{cite journal|last1=Lupa|first1=MT|last2=Caldwell|first2=JH|title=Effect of Agrin on the Distribution of Acetylcholine Receptors and Sodium Channels on Adult Skeletal Muscle Fibers in Culture|journal=Journal of Cell Biology|date=Nov 1991|volume=115|issue=3|pages=765–778|pmid=1655812|doi=10.1083/jcb.115.3.765|pmc=2289169}}</ref>