Editing Depolarization (section)

==Physiology==
{{unreferenced section|date=February 2015}}
The process of depolarization is entirely dependent upon the intrinsic electrical nature of most cells. When a cell is at rest, the cell maintains what is known as a [[resting potential]].<ref name=":0">{{Citation |last=Chrysafides |first=Steven M. |title=Physiology, Resting Potential |date=2025 |work=StatPearls |url=https://www.ncbi.nlm.nih.gov/books/NBK538338/#:~:text=Introduction,in%20a%20non-excited%20state. |access-date=2025-04-06 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=30855922 |last2=Bordes |first2=Stephen J. |last3=Sharma |first3=Sandeep}}</ref> The resting potential generated by nearly all cells results in the interior of the cell having a negative charge compared to the exterior of the cell.<ref name=":0" /> To maintain this electrical imbalance, [[ion]]s are transported across the cell's plasma membrane.<ref>{{Citation |last=Purves |first=Dale |title=The Ionic Basis of the Resting Membrane Potential |date=2001 |work=Neuroscience. 2nd edition |url=https://www.ncbi.nlm.nih.gov/books/NBK10931/ |access-date=2024-08-18 |publisher=Sinauer Associates |language=en |last2=Augustine |first2=George J. |last3=Fitzpatrick |first3=David |last4=Katz |first4=Lawrence C. |last5=LaMantia |first5=Anthony-Samuel |last6=McNamara |first6=James O. |last7=Williams |first7=S. Mark}}</ref> The transport of the ions across the plasma membrane is accomplished through several different types of transmembrane proteins embedded in the cell's plasma membrane that function as pathways for ions both into and out of the cell, such as [[ion channel]]s, [[sodium potassium pump]]s, and [[voltage-gated ion channel]]s.<ref>{{Citation |last=Cooper |first=Geoffrey M. |title=Transport of Small Molecules |date=2000 |work=The Cell: A Molecular Approach. 2nd edition |url=https://www.ncbi.nlm.nih.gov/books/NBK9847/#:~:text=The%20flow%20of%20ions%20through%20membrane%20channels%20is%20dependent%20on,than%20in%20the%20surrounding%20medium. |access-date=2025-04-06 |publisher=Sinauer Associates |language=en}}</ref>

===Resting potential===
The resting potential must be established within a cell before the cell can be depolarized. There are many mechanisms by which a cell can establish a resting potential, however there is a typical pattern of generating this resting potential that many cells follow. The generation of a negative resting potential within the cell involves the utilization of ion channels, ion pumps, and voltage-gated ion channels by the cell.<ref>{{Citation |last1=Chrysafides |first1=Steven M. |title=Physiology, Resting Potential |date=2024 |work=StatPearls |url=http://www.ncbi.nlm.nih.gov/books/NBK538338/ |access-date=2024-03-07 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=30855922 |last2=Bordes |first2=Stephen J. |last3=Sharma |first3=Sandeep}}</ref> However, the process of generating the resting potential within the cell also creates an environment outside the cell that favors depolarization. The [[sodium potassium pump]] is largely responsible for the optimization of conditions on both the interior and the exterior of the cell for depolarization.

By pumping three positively charged sodium ions (Na<sup>+</sup>) out of the cell for every two positively charged potassium ions (K<sup>+</sup>) pumped into the cell, not only is the resting potential of the cell established, but an unfavorable [[concentration gradient]] is created by increasing the concentration of sodium outside the cell and increasing the concentration of potassium within the cell.<ref>{{Citation |last1=Pirahanchi |first1=Yasaman |title=Physiology, Sodium Potassium Pump |date=2024 |work=StatPearls |url=http://www.ncbi.nlm.nih.gov/books/NBK537088/ |access-date=2024-03-07 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=30725773 |last2=Jessu |first2=Rishita |last3=Aeddula |first3=Narothama R.}}
</ref> While there is an excessive amount of potassium in the cell and sodium outside the cell, the generated resting potential maintains the closure of voltage-gated ion channels in the plasma membrane. This not only prevents the diffusion of ions pumped across the membrane but also involves the activity of potassium leak channels, allowing a controlled passive efflux of potassium ions, which contributes to the establishment of the negative resting potential.<ref name="Alberts" /> Additionally, despite the high concentration of positively-charged potassium ions, most cells contain internal components (of negative charge), which accumulate to establish a negative inner charge.

===Depolarization===
[[File:Sodium channel open closed.jpg|thumb|upright|[[Sodium channel#Voltage-gated sodium channels|Voltage-gated sodium channel]]. Open channel ''(top)'' carries an influx of Na<sup>+</sup> ions, giving rise to depolarization. As the channel becomes closed/inactivated ''(bottom)'', the depolarization ends.]]

After a cell has established a resting potential, that cell has the capacity to undergo depolarization. Depolarization is the process by which the membrane potential becomes less negative, facilitating the generation of an action potential.<ref name="Alberts">{{Citation |last1=Alberts |first1=Bruce |title=Ion Channels and the Electrical Properties of Membranes |date=2002 |work=Molecular Biology of the Cell. 4th edition |url=https://www.ncbi.nlm.nih.gov/books/NBK26910/ |access-date=2024-03-07 |publisher=Garland Science |language=en |last2=Johnson |first2=Alexander |last3=Lewis |first3=Julian |last4=Raff |first4=Martin |last5=Roberts |first5=Keith |last6=Walter |first6=Peter}}
</ref> For this rapid change to take place within the interior of the cell, several events must occur along the plasma membrane of the cell.

While the sodium–potassium pump continues to work, the [[Sodium channel#Voltage-gated sodium channels|voltage-gated sodium]] and [[Voltage-gated calcium channel|calcium channels]]<ref>Shah, V. N., Chagot, B., & Chazin, W. J. (2006). Calcium-Dependent Regulation of Ion Channels. Calcium binding proteins, 1(4), 203–212.
</ref> that had been closed while the cell was at resting potential are opened in response to an initial change in voltage.<ref name="Alberts" /> As a change in the neuronal charge leads to the opening of voltage-gated sodium channels, this results in an influx of sodium ions down their [[electrochemical gradient]]. Sodium ions enter the cell, and they contribute a positive charge to the cell interior, causing a change in the membrane potential from negative to positive. The initial sodium ion influx triggers the opening of additional sodium channels ([[Positive feedback|positive-feedback loop]]), leading to further sodium ion transfer into the cell and sustaining the depolarization process until the positive equilibrium potential is reached.<ref>{{Citation |last1=Grider |first1=Michael H. |title=Physiology, Action Potential |date=2024 |work=StatPearls |url=http://www.ncbi.nlm.nih.gov/books/NBK538143/ |access-date=2024-03-07 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=30844170 |last2=Jessu |first2=Rishita |last3=Kabir |first3=Rian}}</ref>

Sodium channels possess an inherent inactivation mechanism that prompts rapid reclosure, even as the membrane remains depolarized. During this equilibrium, the sodium channels enter an inactivated state, temporarily halting the influx of sodium ions until the membrane potential becomes negatively charged again. Once the cell's interior is sufficiently positively charged, depolarization concludes, and the channels close once more.<ref name="Alberts" />

===Repolarization===

After a cell has been depolarized, it undergoes one final change in internal charge. Following depolarization, the voltage-gated sodium ion channels that had been open while the cell was undergoing depolarization close again. The increased positive charge within the cell now causes the potassium channels to open. Potassium ions (K<sup>+</sup>) begin to move down the electrochemical gradient (in favor of the concentration gradient and the newly established electrical gradient). As potassium moves out of the cell the potential within the cell decreases and approaches its resting potential once more. The sodium potassium pump works continuously throughout this process.<ref>{{cite book|last1=Lodish|first1=H|last2=Berk|first2=A|last3=Kaiser|first3=C|last4=Krieger|first4=M|last5=Bretscher|first5=A|last6=Ploegh|first6=H|last7=Amon|first7=A|title=Molecular Cell Biology|url=https://archive.org/details/molecularcellbio00lodi|url-access=registration|date=2000|publisher=W. H. Freeman and Company|location=New York, NY|pages=[https://archive.org/details/molecularcellbio00lodi/page/1021 1021]–1022, 1025, 1045|edition=7th|isbn=978-0-7167-3136-8}}</ref>
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