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Patch clamp
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=== Cell-attached patch === [[File:Cell-Attached Patch Clamp.png|thumb|right|Cell-attached patch configuration]] For this method, the pipette is sealed onto the cell membrane to obtain a gigaseal (a seal with electrical resistance on the order of a gigaohm), while ensuring that the cell membrane remains intact. This allows the recording of currents through single, or a few, ion channels contained in the patch of membrane captured by the pipette. By only attaching to the exterior of the cell membrane, there is very little disturbance of the cell structure.<ref name=Sakamann /> Also, by not disrupting the interior of the cell, any intracellular mechanisms normally influencing the channel will still be able to function as they would physiologically.<ref name="Hamill, et al - Outside-out">{{cite journal |author=Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ. |title=Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches |journal=Pflügers Archiv: European Journal of Physiology |year=1981 |volume=391 |issue=2 |pages=85–100 |doi=10.1007/BF00656997 |pmid=6270629|last2=Marty |last3=Neher |last4=Sakmann |last5=Sigworth |citeseerx=10.1.1.456.107 |s2cid=12014433 }}</ref> Using this method it is also relatively easy to obtain the right configuration, and once obtained it is fairly stable.<ref name=Molleman >{{cite book|last1=Molleman|first1=Areles|title=Patch Clamping: An Introductory Guide To Patch Clamp Electrophysiology|date=March 6, 2003|publisher=Wiley|isbn=9780470856529|doi=10.1002/0470856521}}</ref> For [[ligand-gated ion channels]] or channels that are modulated by [[receptor (biochemistry)#Metabotropic receptors|metabotropic receptors]], the [[neurotransmitter]] or drug being studied is usually included in the pipette solution, where it can interact with what used to be the external surface of the membrane. The resulting channel activity can be attributed to the drug being used, although it is usually not possible to then change the drug concentration inside the pipette. The technique is thus limited to one point in a [[dose-response relationship|dose response curve]] per patch. Therefore, the dose response is accomplished using several cells and patches. However, [[voltage-gated ion channel]]s can be clamped successively at different membrane potentials in a single patch. This results in channel activation as a function of voltage, and a complete [[Ohm's law|I-V (current-voltage) curve]] can be established in only one patch. Another potential drawback of this technique is that, just as the intracellular pathways of the cell are not disturbed, they cannot be directly modified either.<ref name=Molleman />
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