98:(Na) and potassium ions inside and outside the cell are moved by a sodium potassium pump, ensuring that electrochemical equilibrium remains unreached to allow the cell to maintain a state of resting membrane potential. In the graph of an action potential, the hyper-polarization section looks like a downward dip that goes lower than the line of resting membrane potential. In this afterhyperpolarization (the downward dip), the cell sits at more negative potential than rest (about −80 mV) due to the slow inactivation of voltage gated K delayed rectifier channels, which are the primary K channels associated with repolarization. At these low voltages, all of the
151:), Na channels have faster kinetics and activate/deinactivate much more quickly. Repolarization occurs as the influx of Na decreases (channels deinactivate) and the efflux of K ions increases as its channels open. The decreased conductance of sodium ions and increased conductance of potassium ions cause the cell's membrane potential to very quickly return to, and past the resting membrane potential, which causes the hyperpolarization due to the potassium channels closing slowly, allowing more potassium to flow through after the resting membrane potential has been reached.
275:, which are K channels which are activated by increases in Ca 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. Specifically, these channels are activated when Ca binds to
140:. The selectivity of this channel to voltage is mediated by four of these transmembrane domains (S1–S4) – the voltage sensing domain. The other two domains (S5, S6) form the pore by which ions traverse. Activation and deactivation of the voltage gated K channel is triggered by conformational changes in the voltage sensing domain. Specifically, the S4 domain moves such that it activates and deactivates the pore. During activation, there is outward S4 motion, causing tighter VSD-pore linkage. Deactivation is characterized by inward S4 motion.
20:
391:, but the drugs do not provide sufficient protection. Acetazolamide and similar drugs are known to be able to improve the oxygenation and sleep apnea for patients in higher altitudes, but the benefits of the drug have been observed only when traveling at altitudes temporarily, not for people who remain at a higher altitude for a longer time.
279:(CaM) because the N-lobe of CaM interacts with the channel's S4/S5 linker to induce conformational change. 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 Ca ions are exceeded by K ions leaving the cell continuously.
337:
Early repolarization is a phenomenon that can be seen in ECG recordings of ventricular cells where there is an elevated ST segment, also known as a J wave. The J wave is prominent when there is a larger outward current in the epicardium compared to the endocardium. It has been historically considered
239:
4 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 Ca ions entering the cell. When large quantities of Ca ions enter the cell due to
159:
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
369:
Upon being diagnosed, most individuals do not need immediate intervention, as early repolarization on an ECG does not indicate any life-threatening medical emergency. Three to thirteen percent of healthy individuals have been observed to have early repolarization on an ECG. However, patients who
361:
The primary root of early repolarization syndrome stems from malfunctions of electrical conductance in ion channels, which may be due to genetic factors. Malfunctions of the syndrome include fluctuating sodium, potassium, and calcium currents. Changes in these currents may result in overlap of
93:
Repolarization is a stage of an action potential in which the cell experiences a decrease of voltage due to the efflux of potassium (K) ions along its electrochemical gradient. This phase occurs after the cell reaches its highest voltage from depolarization. After repolarization, the cell
123:
are another example of a selective pharmacological blocker for voltage gated K channels. The lack of repolarization means that neuron stays at a high voltage, which slows sodium channel deactivation to a point where there is not enough inwards Na current to depolarize and sustain firing.
386:
can experience impaired cardiac repolarization, increasing the morbidity and mortality of the condition greatly. Especially at higher altitudes, patients are much more susceptible to repolarization disturbances. This can be somewhat mitigated through the use of medications such as
102:
close, and the cell returns to resting potential within a few milliseconds. A cell which is experiencing repolarization is said to be in its absolute refractory period. Other voltage gated K channels which contribute to repolarization include A-type channels and
338:
to be a normal variant in cardiac rhythm but recent studies show that it is related to an increased risk of cardiac arrest. Early repolarization occurs mainly in males and is associated with a larger potassium current caused by the hormone
323:), there are many physiological changes effecting repolarization that will also affect these waves. Apart from changes in the structure of the heart that effect repolarization, there are many pharmaceuticals that have the same effect.
350:
As mentioned in the previous section, early repolarization is known as appearing as elevated wave segments on ECGs. Recent studies have shown a connection between early repolarization and sudden
115:
Blockages in repolarization can arise due to modifications of the voltage-gated K channels. This is demonstrated with selectively blocking voltage gated K channels with the antagonist
374:(ICD) is strongly recommended. In addition, a patient may be more prone to atrial fibrillation if the individual has early repolarization syndrome and is under sixty years of age.
78:
Repolarization typically results from the movement of positively charged K ions out of the cell. The repolarization phase of an action potential initially results in
1251:"Patients with Obstructive Sleep Apnea Have Cardiac Repolarization Disturbances when Travelling to Altitude: Randomized, Placebo-Controlled Trial of Acetazolamide"
334:
to give a normal, upright T-wave, whereas a duration of 20–40 msec would give an isoelectric wave and anything under 20 msec would result in a negative T-wave.
1133:
Hasegawa Y, Watanabe H, Ikami Y, Otsuki S, Iijima K, Yagihara N, et al. (April 2019). "Early repolarization and risk of lone atrial fibrillation".
259:
2 channels were not found to contribute to repolarization rate as blocking these channels did not result in changes in neuron repolarization rates.
1016:
Higuchi T, Nakaya Y (August 1984). "T wave polarity related to the repolarization process of epicardial and endocardial ventricular surfaces".
107:. Protein transport molecules are responsible for Na out of the cell and K into the cell to restore the original resting ion concentrations.
55:
which has changed the membrane potential to a positive value. The repolarization phase usually returns the membrane potential back to the
481:
342:. Additionally, although the risk is unknown, African American individuals seem more likely to have the early repolarization more often.
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myocardial regions undergoing different phases of the action potential simultaneously, leading to risk of ventricular fibrillation and
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channel types in repolarization of the action potential in genetically identified subclasses of pyramidal neurons in mouse neocortex"
1103:
235:
4 channels are associated with the primary repolarization conductance following the depolarization period of a neuron. When the K
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display early repolarization after surviving an event of early repolarization syndrome (a sudden-cardiac death experience), an
330:. In action potentials stimulated on the epicardium, it was found that the duration of the action potential needed to be 40–60
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419:
853:"Small-conductance calcium-activated potassium (SK) channels contribute to action potential repolarization in human atria"
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The switch from depolarization into repolarization is dependent on the kinetic mechanisms of both voltage gated K and
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without other structural heart defects as well as an early depolarization pattern, which can be seen on ECG.
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Latshang TD, Kaufmann B, Nussbaumer-Ochsner Y, Ulrich S, Furian M, Kohler M, et al. (September 2016).
977:"Ventricular repolarization components on the electrocardiogram: cellular basis and clinical significance"
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extended repolarization periods, the neuron may die, leading to the development of stroke or seizures.
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3 channels open at a more positive membrane potential and deactivate 10 times faster than the other K
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Purves D, Augustine GJ, Fitzpatrick D, Katz LC, LaMantia AS, McNamara JO, Williams SM, eds. (2001).
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the repolarization of the cell membrane to re-establish the resting potential. The four types are K
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383:
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On top of that, repolarization is also altered based on the location and duration of the initial
894:"Activation mechanism of a human SK-calmodulin channel complex elucidated by cryo-EM structures"
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27:. As seen above, repolarization takes place just after the peak of the action potential, when
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311:. Due to the complexity of the heart, specifically how it contains three layers of cells (
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as these regions create microsecond action potentials that requires quick repolarization.
147:. Although both voltage gated Na and K channels activate at roughly the same voltage (−50
8:
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Skibsbye L, Poulet C, Diness JG, Bentzen BH, Yuan L, Kappert U, et al. (July 2014).
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3 Channels: Enablers of Rapid Firing, Neurotransmitter
Release, and Neuronal Endurance"
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354:, which is identified as early repolarization syndrome. The condition is shown in both
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Bourier F, Denis A, Cheniti G, Lam A, Vlachos K, Takigawa M, et al. (2018).
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1178:"The early repolarization and pattern syndrome: from ECG criteria to management"
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results in the falling phase of an action potential. The ions pass through the
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channels. These properties allow for the high-frequency firing that mammalian
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Jensen MØ, Jogini V, Borhani DW, Leffler AE, Dror RO, Shaw DE (April 2012).
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Another type of K channel that helps to mediate repolarization in the human
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Utilizing voltage-clamp data from experiments based on rodent neurons, the K
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hyperpolarizes as it reaches resting membrane potential (−70 mV in neuron).
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119:(TEA). By blocking the channel, repolarization is effectively stopped.
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4 channels are blocked, the action potential predictably widens. The K
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1 channel primarily influences the repolarization of the axon. The K
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28:
1200:"Early Repolarization Syndrome: Diagnostic and Therapeutic Approach"
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Yan GX, Lankipalli RS, Burke JF, Musco S, Kowey PR (August 2003).
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1053:"Early repolarization syndrome: A cause of sudden cardiac death"
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Impaired cardiac repolarization with obstructive sleep apnea
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4 channels are characteristically activated rapidly. When K
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The structure of the voltage gated K channel is that of six
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Hirokawa N, Windhorst U (2008). "Depolarization Block".
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1 channels are found to contribute to repolarization of
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2 channel is characteristically activated slower. The K
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708:"Chapter Two: Ionic Mechanisms and Action Potentials"
414:. Benjamin-Cummings Publishing Company. p. 389.
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Hardin J, Bertoni GP, Kleinsmith LJ (December 2010).
90:. Repolarization usually takes several milliseconds.
650:"Mechanism of voltage gating in potassium channels"
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47:that returns it to a negative value just after the
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505:(2nd ed.). Sunderland, Mass: Sinauer Assoc.
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251:, likely associated with an upregulation of the K
82:, attainment of a membrane potential, termed the
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957:. University of Kansas Department of Physiology
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599:Kuang Q, Purhonen P, Hebert H (October 2015).
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1305:. Psychology Department, Hanover College
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1051:Ali A, Butt N, Sheikh AS (August 2015).
729:. New York, NY: Oxford University Press.
291:, repolarization can be seen on an ECG (
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798:Kaczmarek LK, Zhang Y (October 2017).
372:implantable cardioverter-defibrillator
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553:Fundamentals of Human Neuropsychology
111:Deviations from normal repolarization
1204:Frontiers in Cardiovascular Medicine
605:Cellular and Molecular Life Sciences
155:Type of K channels in repolarization
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601:"Structure of potassium channels"
555:. New York, NY: Worth Publishers.
435:Chrysafides SM, Sharma S (2019).
86:, that is more negative than the
892:Lee CH, MacKinnon R (May 2018).
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480:Lentz TL, Erulkar SD (2018).
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346:Early repolarization syndrome
263:Repolarization of atria cells
1303:"Repolarization (Animation)"
1030:10.1016/0002-8703(84)90614-8
568:Encyclopedia of Neuroscience
16:Change in membrane potential
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1057:World Journal of Cardiology
551:Whishaw IQ, Kolb B (2015).
208:require. Areas with dense K
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755:Journal of Neurophysiology
411:Becker's World of the Cell
283:Ventricular repolarization
128:Voltage gated K mechanisms
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31:ions rush out of the cell.
617:10.1007/s00018-015-1948-5
441:. StatPearls Publishing.
382:Patients who suffer from
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100:voltage gated K channels
43:refers to the change in
23:A labeled diagram of an
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857:Cardiovascular Research
674:10.1126/science.1216533
486:Encyclopædia Britannica
384:obstructive sleep apnea
212:3 channels include the
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808:Physiological Reviews
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725:Striedter GF (2016).
134:transmembrane helices
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747:"Roles of specific K
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910:2018Sci...360..508L
712:Neuroscience Online
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527:"Action Potential"
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961:2019-09-25
537:2019-09-26
395:References
321:epicardium
317:myocardium
301:ST segment
299:(Osborn),
295:) via the
289:ventricles
277:calmodulin
273:SK channel
222:brain stem
136:along the
706:Byrn JH.
465:ignored (
455:cite book
214:neocortex
73:K channel
61:potassium
1285:27306264
1236:30542653
1163:58641364
1155:30661277
1089:26322186
1003:12906963
936:29724949
879:24817686
838:28904001
785:26864770
682:22499946
635:26070303
447:30855922
176:4. The K
1276:4989251
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1080:4549780
1038:6464965
927:6241251
906:Bibcode
898:Science
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776:4922457
690:2340286
662:Bibcode
654:Science
626:4565861
271:is the
206:neurons
192:2 and K
172:3 and K
71:of the
1309:18 May
1283:
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309:U wave
305:T wave
297:J-wave
96:Sodium
75:pore.
1255:Sleep
1159:S2CID
686:S2CID
269:atria
243:The K
1311:2013
1281:PMID
1232:PMID
1151:PMID
1115:2019
1085:PMID
1034:PMID
999:PMID
932:PMID
875:PMID
834:PMID
781:PMID
678:PMID
631:PMID
580:ISBN
507:ISBN
467:help
443:PMID
416:ISBN
332:msec
319:and
307:and
224:and
168:2, K
164:1, K
65:ions
63:(K)
1271:PMC
1263:doi
1222:PMC
1212:doi
1143:doi
1075:PMC
1065:doi
1026:doi
1022:108
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