Repolarization

== Type of K⁺ channels in repolarization ==

== Type of K⁺ channels in repolarization ==

Following the action potential, characteristically generated by the influx of Na⁺ through voltage gated Na⁺ channels, there is a period of repolarization in which the Na⁺ channels are inactivated while K⁺ channels are activated. Further study of K⁺ channels shows that there are four types which influence the repolarization of the cell membrane to re-establish the resting potential. The four types are K_v1, K_v2, K_v3 and K_v4. The K_v1 channel primarily influences the repolarization of the axon. The K_v2 channel is characteristically activated slower. The K_v4 channels are characteristically activated rapidly. When K_v2 and K_v4 channels are blocked, the action potential predictably widens.{{cite journal | vauthors = Pathak D, Guan D, Foehring RC | title = Roles of specific K_v channel types in repolarization of the action potential in genetically identified subclasses of pyramidal neurons in mouse neocortex | journal = Journal of Neurophysiology | volume = 115 | issue = 5 | pages = 2317–29 | date = May 2016 | pmid = 26864770 | pmc = 4922457 | doi = 10.1152/jn.01028.2015 }} The K_v3 channels open at a more positive membrane potential and deactivate 10 times faster than the other K_v channels. These properties allow for the high-frequency firing that mammalian [[neuron]]s require. Areas with dense K_v3 channels include the [[neocortex]], [[basal ganglia]], [[brain stem]] and [[hippocampus]] as these regions create microsecond action potentials that requires quick repolarization.{{cite journal | vauthors = Kaczmarek LK, Zhang Y | title = K_v3 Channels: Enablers of Rapid Firing, Neurotransmitter Release, and Neuronal Endurance | journal = Physiological Reviews | volume = 97 | issue = 4 | pages = 1431–1468 | date = October 2017 | pmid = 28904001 | pmc = 6151494 | doi = 10.1152/physrev.00002.2017 }}

Following the action potential, characteristically generated by the influx of Na⁺ through voltage gated Na⁺ channels, there is a period of repolarization in which the Na⁺ channels are inactivated while K⁺ channels are activated. Further study of K⁺ channels shows that there are four types which influence the repolarization of the [[cell membrane]] to re-establish the resting potential. The four types are K_v1, K_v2, K_v3 and K_v4. The K_v1 channel primarily influences the repolarization of the axon. The K_v2 channel is characteristically activated slower. The K_v4 channels are characteristically activated rapidly. When K_v2 and K_v4 channels are blocked, the action potential predictably widens.{{cite journal | vauthors = Pathak D, Guan D, Foehring RC | title = Roles of specific K_v channel types in repolarization of the action potential in genetically identified subclasses of pyramidal neurons in mouse neocortex | journal = Journal of Neurophysiology | volume = 115 | issue = 5 | pages = 2317–29 | date = May 2016 | pmid = 26864770 | pmc = 4922457 | doi = 10.1152/jn.01028.2015 }} The K_v3 channels open at a more positive membrane potential and deactivate 10 times faster than the other K_v channels. These properties allow for the high-frequency firing that mammalian [[neuron]]s require. Areas with dense K_v3 channels include the [[neocortex]], [[basal ganglia]], [[brain stem]] and [[hippocampus]] as these regions create microsecond action potentials that requires quick repolarization.{{cite journal | vauthors = Kaczmarek LK, Zhang Y | title = K_v3 Channels: Enablers of Rapid Firing, Neurotransmitter Release, and Neuronal Endurance | journal = Physiological Reviews | volume = 97 | issue = 4 | pages = 1431–1468 | date = October 2017 | pmid = 28904001 | pmc = 6151494 | doi = 10.1152/physrev.00002.2017 }}

Utilizing voltage-clamp data from experiments based on rodent neurons, the K_v4 channels are associated with the primary repolarization conductance following the depolarization period of a neuron. When the K_v4 channel is blocked, the action potential becomes broader, resulting in an extended repolarization period, delaying the neuron from being able to fire again. The rate of repolarization closely regulates the amount of Ca²⁺ ions entering the cell. When large quantities of Ca²⁺ ions enter the cell due to extended repolarization periods, the neuron may die, leading to the development of stroke or seizures.

Utilizing voltage-clamp data from experiments based on [[rodent]] neurons, the K_v4 channels are associated with the primary repolarization conductance following the depolarization period of a neuron. When the K_v4 channel is blocked, the action potential becomes broader, resulting in an extended repolarization period, delaying the neuron from being able to fire again. The rate of repolarization closely regulates the amount of Ca²⁺ ions entering the cell. When large quantities of Ca²⁺ ions enter the cell due to extended repolarization periods, the neuron may die, leading to the development of stroke or seizures.

The K_v1 channels are found to contribute to repolarization of [[Pyramidal cell|pyramidal neurons]], likely associated with an upregulation of the K_v4 channels. The K_v2 channels were not found to contribute to repolarization rate as blocking these channels did not result in changes in neuron repolarization rates.

The K_v1 channels are found to contribute to repolarization of [[Pyramidal cell|pyramidal neurons]], likely associated with an upregulation of the K_v4 channels. The K_v2 channels were not found to contribute to repolarization rate as blocking these channels did not result in changes in neuron repolarization rates.

== Repolarization of atria cells ==

== Repolarization of atria cells ==

Another type of K⁺ channel that helps to mediate repolarization in the human [[Atrium (heart)|atria]] is the [[SK channel]], which are K⁺ channels which are activated by increases in Ca²⁺ concentration. "SK channel" stands for a small conductance calcium activated potassium channel, and the channels are found in the heart. SK channels specifically act in the right atrium of the heart, and have not been found to be functionally important in the ventricles of the human heart. The channels are active during repolarization as well as during the atrial diastole phase when the current undergoes hyperpolarization.{{cite journal | vauthors = Skibsbye L, Poulet C, Diness JG, Bentzen BH, Yuan L, Kappert U, Matschke K, Wettwer E, Ravens U, Grunnet M, Christ T, Jespersen T | display-authors = 6 | title = Small-conductance calcium-activated potassium (SK) channels contribute to action potential repolarization in human atria | journal = Cardiovascular Research | volume = 103 | issue = 1 | pages = 156–67 | date = July 2014 | pmid = 24817686 | doi = 10.1093/cvr/cvu121 | doi-access = free }} Specifically, these channels are activated when Ca²⁺ binds to [[calmodulin]] (CaM) because the N-lobe of CaM interacts with the channel's S4/S5 linker to induce conformational change.{{cite journal | vauthors = Lee CH, MacKinnon R | title = Activation mechanism of a human SK-calmodulin channel complex elucidated by cryo-EM structures | journal = Science | volume = 360 | issue = 6388 | pages = 508–513 | date = May 2018 | pmid = 29724949 | pmc = 6241251 | doi = 10.1126/science.aas9466 | bibcode = 2018Sci...360..508L }} When these K⁺ channels are activated, the K⁺ ions rush out of the cell during the peak of its action potential causing the cell to repolarize as the influx of Ca²⁺ ions are exceeded by K⁺ ions leaving the cell continuously.{{cite web | first = Scott | last = Goodman | name-list-style = vanc |url= https://www.kumc.edu/AMA-MSS/Study/phys2.htm |work=Physiology Medical Study Guides | title = Cardiovascular |publisher = University of Kansas Department of Physiology |access-date=2019-09-25 }}

Another type of K⁺ channel that helps to mediate repolarization in the human [[Atrium (heart)|atria]] is the [[SK channel]], which are K⁺ channels which are activated by increases in Ca²⁺ concentration. "SK channel" stands for a small conductance calcium activated potassium channel, and the channels are found in the heart. SK channels specifically act in the right atrium of the heart, and have not been found to be functionally important in the ventricles of the human heart. The channels are active during repolarization as well as during the atrial diastole phase when the current undergoes hyperpolarization.{{cite journal | vauthors = Skibsbye L, Poulet C, Diness JG, Bentzen BH, Yuan L, Kappert U, Matschke K, Wettwer E, Ravens U, Grunnet M, Christ T, Jespersen T | display-authors = 6 | title = Small-conductance calcium-activated potassium (SK) channels contribute to action potential repolarization in human atria | journal = Cardiovascular Research | volume = 103 | issue = 1 | pages = 156–67 | date = July 2014 | pmid = 24817686 | doi = 10.1093/cvr/cvu121 | doi-access = free }} Specifically, these channels are activated when Ca²⁺ binds to [[calmodulin]] (CaM) because the N-lobe of CaM interacts with the channel's S4/S5 linker to induce [[conformational change]].{{cite journal | vauthors = Lee CH, MacKinnon R | title = Activation mechanism of a human SK-calmodulin channel complex elucidated by cryo-EM structures | journal = Science | volume = 360 | issue = 6388 | pages = 508–513 | date = May 2018 | pmid = 29724949 | pmc = 6241251 | doi = 10.1126/science.aas9466 | bibcode = 2018Sci...360..508L }} When these K⁺ channels are activated, the K⁺ ions rush out of the cell during the peak of its action potential causing the cell to repolarize as the influx of Ca²⁺ ions are exceeded by K⁺ ions leaving the cell continuously.{{cite web | first = Scott | last = Goodman | name-list-style = vanc |url= https://www.kumc.edu/AMA-MSS/Study/phys2.htm |work=Physiology Medical Study Guides | title = Cardiovascular |publisher = University of Kansas Department of Physiology |access-date=2019-09-25 }}

== Ventricular repolarization ==

== Ventricular repolarization ==