270:
is recorded downstream from the triggering impulse. The stimulus is automatically decreased in steps of a set percentage until the response falls below the target (generation of an action potential). Thereafter, the stimulus is stepped up or down depending on whether the previous response was lesser or greater than the target response until a resting (or control) threshold has been established. Nerve excitability can then be changed by altering the nerve environment or applying additional currents. Since the value of a single threshold current provides little valuable information because it varies within and between subjects, pairs of threshold measurements, comparing the control threshold to thresholds produced by refractoriness, supernormality, strength-duration time constant or "threshold electrotonus" are more useful in scientific and clinical study.
153:, the threshold potential's conditions exhibited a balance of currents that were unstable. Instability refers to the fact that any further depolarization activates even more voltage-gated sodium channels, and the incoming sodium depolarizing current overcomes the delayed outward current of potassium. At resting level, on the other hand, the potassium and sodium currents are equal and opposite in a stable manner, where a sudden, continuous flow of ions should not result. The basis is that at a certain level of depolarization, when the currents are equal and opposite in an unstable manner, any further entry of positive charge generates an action potential. This specific value of depolarization (in mV) is otherwise known as the threshold potential.
237:
within the axon all affect the threshold value. Typically in the axon or dendrite, there are small depolarizing or hyperpolarizing signals resulting from a prior stimulus. The passive spread of these signals depend on the passive electrical properties of the cell. The signals can only continue along the neuron to cause an action potential further down if they are strong enough to make it past the cell's membrane resistance and capacitance. For example, a neuron with a large diameter has more ionic channels in its membrane than a smaller cell, resulting in a lower resistance to the flow of ionic current. The current spreads quicker in a cell with less resistance, and is more likely to reach the threshold at other portions of the neuron.
223:. More sodium is outside the cell relative to the inside, and the positive charge within the cell propels the outflow of potassium ions through delayed-rectifier voltage-gated potassium channels. Since the potassium channels within the cell membrane are delayed, any further entrance of sodium activates more and more voltage-gated sodium channels. Depolarization above threshold results in an increase in the conductance of Na sufficient for inward sodium movement to swamp outward potassium movement immediately. If the influx of sodium ions fails to reach threshold, then sodium conductance does not increase a sufficient amount to override the resting potassium conductance. In that case,
290:, which uses the threshold tracking set-up to produce long-lasting subthreshold depolarizing or hyperpolarizing currents within a membrane. Changes in cell excitability can be observed and recorded by creating these long-lasting currents. Threshold decrease is evident during extensive depolarization, and threshold increase is evident with extensive hyperpolarization. With hyperpolarization, there is an increase in the resistance of the internodal membrane due to closure of potassium channels, and the resulting plot "fans out". Depolarization produces has the opposite effect, activating potassium channels, producing a plot that "fans in".
205:. Leak potassium channels allow potassium to flow through the membrane in response to the disparity in concentrations of potassium inside (high concentration) and outside the cell (low). The loss of positive(+) charges of the potassium(K+) ions from the inside of the cell results in a negative potential there compared to the extracellular surface of the membrane. A much smaller "leak" of sodium(Na+) into the cell results in the actual resting potential, about –70 mV, being less negative than the calculated potential for K+ alone, the equilibrium potential, about –90 mV. The
401:, found in fish oils and several plant oils, serve a role in the prevention of arrhythmias. By inhibiting the voltage-dependent sodium current, these oils shift the threshold potential to a more positive value; therefore, an action potential requires increased depolarization. Clinically therapeutic use of these extracts remains a subject of research, but a strong correlation is established between regular consumption of fish oil and lower frequency of hospitalization for atrial fibrillation, a severe and increasingly common arrythmia.
20:
249:
ions across the membrane by opening and letting potassium flow down its concentration gradient from inside to outside the cell. They close slowly as well, resulting in an outward flow of positive charge that exceeds the balance necessary. It results in excess negativity in the cell, requiring an extremely large stimulus and resulting depolarization to cause a response.
293:
The most important factor determining threshold electrotonus is membrane potential, so threshold electrotonus can also be used as an index of membrane potential. Furthermore, it can be used to identify characteristics of significant medical conditions through comparing the effects of those conditions
248:
that makes it much more difficult to reach threshold. The delayed-rectifier potassium channels are responsible for the late outward phase of the action potential, where they open at a different voltage stimulus compared to the quickly activated sodium channels. They rectify, or repair, the balance of
269:
Threshold tracking allows for the strength of a test stimulus to be adjusted by a computer in order to activate a defined fraction of the maximal nerve or muscle potential. A threshold tracking experiment consists of a 1-ms stimulus being applied to a nerve in regular intervals. The action potential
117:
applied this concept in experiments to discover nervous excitability, and concluded that the local excitatory process through a semi-permeable membrane depends upon the ionic concentration. Also, ion concentration was shown to be the limiting factor in excitation. If the proper concentration of ions
167:
The threshold value controls whether or not the incoming stimuli are sufficient to generate an action potential. It relies on a balance of incoming inhibitory and excitatory stimuli. The potentials generated by the stimuli are additive, and they may reach threshold depending on their frequency and
145:
generally exhibit the phenomenon that a certain membrane potential must be reached in order to fire an action potential. Since the experiment yielded results through the observation of ionic conductance changes, Hodgkin and Huxley used these terms to discuss the threshold potential. They initially
363:
Since the 1940s, the concept of diastolic depolarization, or "pacemaker potential", has become established; this mechanism is a characteristic distinctive of cardiac tissue. When the threshold is reached and the resulting action potential fires, a heartbeat results from the interactions; however,
236:
The value of threshold can vary according to numerous factors. Changes in the ion conductances of sodium or potassium can lead to either a raised or lowered value of threshold. Additionally, the diameter of the axon, density of voltage activated sodium channels, and properties of sodium channels
227:
are observed in some type of neurons. If successful, the sudden influx of positive charge depolarizes the membrane, and potassium is delayed in re-establishing, or hyperpolarizing, the cell. Sodium influx depolarizes the cell in attempt to establish its own equilibrium potential (about +52 mV) to
261:
and changes in this potential. These tests can measure and compare a control threshold (or resting threshold) to a threshold produced by a change in the environment, by a preceding single impulse, an impulse train, or a subthreshold current. Measuring changes in threshold can indicate changes in
354:
patients. While the mechanism ultimately responsible for the variance differs between the two conditions, tests through a response to ischemia indicate a similar resistance, ironically, to ischemia and resulting paresthesias. As ischemia occurs through inhibition of the sodium-potassium pump,
277:
techniques, like the constant stimulus method. This technique can track threshold changes within a dynamic range of 200% and in general give more insight into axonal properties than other tests. Also, this technique allows for changes in threshold to be given a quantitative value, which when
380:
as a side effect. Prolongation of this interval is a result of a delay in sodium and calcium channel inactivation; without proper channel inactivation, the threshold potential is reached prematurely and thus arrhythmia tends to result. These drugs, known as pro-arrhythmic agents, include
184:, or attempt to reach threshold. The task of depolarization requires several key steps that rely on anatomical factors of the cell. The ion conductances involved depend on the membrane potential and also the time after the membrane potential changes.
385:. The use of such agents is particularly frequent in intensive care units, and special care must be exercised when QT intervals are prolonged in such patients: arrhythmias as a result of prolonged QT intervals include the potentially fatal
200:
is, in itself, highly impermeable to ions. The complete structure of the cell membrane includes many proteins that are embedded in or completely cross the lipid bilayer. Some of those proteins allow for the highly specific passage of ions,
218:
However, once a stimulus activates the voltage-gated sodium channels to open, positive sodium ions flood into the cell and the voltage increases. This process can also be initiated by ligand or neurotransmitter binding to a
209:
is an active transporter within the membrane that pumps potassium (2 ions) back into the cell and sodium (3 ions) out of the cell, maintaining the concentrations of both ions as well as preserving the voltage polarization.
333:
in rat cortical neurons after induction of febrile body temperatures; a notable decrease in threshold potential was observed. The mechanism for this decrease possibly involves suppression of inhibition mediated by the
893:
Savelieva, I; Kourliouros, Antonios; Camm, John (2010). "Primary and secondary prevention of atrial fibrillation with statins and polyunsaturated fatty acids: review of evidence and clinical relevance".
240:
The threshold potential has also been shown experimentally to adapt to slow changes in input characteristics by regulating sodium channel density as well as inactivating these sodium channels overall.
298:
and depolarization cause the same "fanning in" effect of the electrotonus waveforms. This observation leads to the conclusion that ischemia may result from over-activation of potassium channels.
146:
suggested that there must be a discontinuity in the conductance of either sodium or potassium, but in reality both conductances tended to vary smoothly along with the membrane potential.
278:
mathematically converted into a percentage, can be used to compare single fiber and multifiber preparations, different neuronal sites, and nerve excitability in different species.
149:
They soon discovered that at threshold potential, the inward and outward currents, of sodium and potassium ions respectively, were exactly equal and opposite. As opposed to the
306:
The role of the threshold potential has been implicated in a clinical context, namely in the functioning of the nervous system itself as well as in the cardiovascular system.
113:
Initial experiments revolved around the concept that any electrical change that is brought about in neurons must occur through the action of ions. The German physical chemist
322:, occurring most commonly in early childhood. Repeated episodes of childhood febrile seizures are associated with an increased risk of temporal lobe epilepsy in adulthood.
257:
Threshold tracking techniques test nerve excitability, and depend on the properties of axonal membranes and sites of stimulation. They are extremely sensitive to the
176:
of synaptic inputs made largely onto a neuron's dendritic tree. These local graded potentials, which are primarily associated with external stimuli, reach the
224:
775:
Monfredi, O; Dobrzyński, H; Mondal, T; Boyett, MR; Morris, GM (2010). "The
Anatomy and Physiology of the Sinoatrial Node—A Contemporary Review".
1054:
942:
722:
1009:
Wang, Y; Qin, J; Han, Y; Cai, J; Xing, G (2011). "Hyperthermia induces epileptiform discharges in cultured rat cortical neurons".
852:"The effect upon the threshold for nervous excitation of the length of nerve exposed, and the angle between current and nerve"
245:
26:
A schematic view of an idealized action potential illustrates its various phases as the action potential passes a point on a
709:
Bostock, Hugh; Cikurel, Katia; Burke, David (1998). "Threshold tracking techniques in the study of human peripheral nerve".
347:
85:'s resting membrane potential (–70 mV) can be altered to either increase or decrease likelihood of reaching threshold via
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241:
173:
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102:
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Actual recordings of action potentials are often distorted compared to the schematic view because of variations in
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were also able to experimentally determine the mechanism behind the threshold for excitation. It is known as the
71:
134:
220:
653:
177:
169:
67:
812:
Nelson, S; Leung, J (2011). "QTc
Prolongation in the Intensive Care Unit: A Review of Offending Agents".
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118:
was attained, excitation would certainly occur. This was the basis for discovering the threshold value.
97:
can depolarize the membrane past threshold and thus excite it while an efflux of potassium or influx of
1062:
274:
841:
Nicholls, J. G.; Martin, A. R.; Fuchs, P. A.; Brown, D. A.; Diamond, M. E.; Weisblat, D. A. (2012).
386:
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and build until they manage to reach the threshold value. The larger the stimulus, the greater the
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763:
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142:
126:
51:
996:
Trautwein, W (1963). "Generation and conduction of impulses in the heart as affected by drugs".
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when this heartbeat occurs at an irregular time, a potentially serious condition known as
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Most often, the threshold potential is a membrane potential value between –50 and –55
19:
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66:, threshold potentials are necessary to regulate and propagate signaling in both the
27:
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Burke, D; Kiernan, Matthew C; Bostock, Hugh (2001). "Excitability of human axons".
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202:
63:
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954:"Action potential initiation and backpropagation in neurons of the mammalian CNS"
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on threshold potential with the effects viewed experimentally. For example,
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10.1002/(SICI)1097-4598(199802)21:2<137::AID-MUS1>3.0.CO;2-C
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554:
263:
86:
82:
845:(5th ed.). Sunderland, Massachusetts: Sinauer Associates, Inc.
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membrane potential, axonal properties, and/or the integrity of the
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make the inside of the cell more positive relative to the outside.
78:
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abnormalities in the threshold potential are hence implicated.
613:
597:
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antimicrobials, antipsychotics, methadone, and, ironically,
346:
Abnormalities in neuronal excitability have been noted in
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497:
458:
446:
105:
the cell and thus inhibit threshold from being reached.
952:
Stuart, G; Spruston, N; Sakmann, B; Häusser, M (1997).
931:
Seifter, Julian; Ratner, Austin; Sloane, David (2005).
141:
techniques on a squid giant axon, they discovered that
93:
ions. An influx of sodium into the cell through open,
244:
by the delayed-rectifier potassium channels causes a
318:, or "fever fit", is a convulsion associated with a
586:
574:
562:
545:
533:
521:
417:
376:A variety of drugs can present prolongation of the
397:Diet may be a variable in the risk of arrhythmia.
896:Naunyn-Schmiedeberg's Archives of Pharmacology
601:
329:recording, an analogous state was replicated
273:Tracking threshold has advantages over other
81:, but can vary based upon several factors. A
8:
225:subthreshold membrane potential oscillations
640:
628:
286:A specific threshold tracking technique is
157:Physiological function and characteristics
875:
509:
482:
18:
429:
410:
338:receptor with excessive heat exposure.
693:Savelieva, Kourliouros & Camm 2010
681:Savelieva, Kourliouros & Camm 2010
38:techniques used to make the recording.
937:. Lippincott Williams & Wilkins.
777:Pacing and Clinical Electrophysiology
168:amplitude. Normal functioning of the
7:
320:significant rise in body temperature
14:
587:Bostock, Cikurel & Burke 1998
575:Burke, Kiernan & Bostock 2001
563:Bostock, Cikurel & Burke 1998
546:Burke, Kiernan & Bostock 2001
534:Bostock, Cikurel & Burke 1998
522:Bostock, Cikurel & Burke 1998
418:Seifter, Ratner & Sloane 2005
50:is the critical level to which a
789:10.1111/j.1540-8159.2010.02838.x
1059:Essentials of Human Physiology
1023:10.1016/j.brainres.2011.08.027
934:Concepts in Medical Physiology
868:10.1113/jphysiol.1927.sp002409
121:Along with reconstructing the
1:
973:10.1016/S0166-2236(96)10075-8
760:10.1016/S1388-2457(01)00595-8
348:amyotrophic lateral sclerosis
95:voltage-gated sodium channels
826:10.1097/NCI.0b013e31822db49d
814:AACN Advanced Critical Care
399:Polyunsaturated fatty acids
163:Summation (neurophysiology)
1111:
1070:Description at cameron.edu
850:Rushton, W. A. H. (1927).
658:American Heart Association
246:relative refractory period
188:Resting membrane potential
160:
151:resting membrane potential
908:10.1007/s00210-009-0468-y
856:The Journal of Physiology
72:peripheral nervous system
1055:"Section 1/1ch4/s1ch4_8"
748:Clinical Neurophysiology
282:"Threshold electrotonus"
16:Critical potential value
998:Pharmacological Reviews
961:Trends in Neurosciences
641:Nelson & Leung 2011
629:Nelson & Leung 2011
207:sodium-potassium ATPase
288:threshold electrotonus
178:axonal initial segment
170:central nervous system
68:central nervous system
39:
654:"Polyunsaturated Fat"
383:antiarrhythmic agents
302:Clinical significance
22:
843:From Neuron to Brain
614:Monfredi et al. 2010
498:Nicholls et al. 2012
459:Nicholls et al. 2012
447:Nicholls et al. 2012
275:electrophysiological
221:ligand-gated channel
194:phospholipid bilayer
135:Hodgkin–Huxley model
36:electrophysiological
695:, pp. 213–215.
387:torsades de pointes
253:Tracking techniques
48:threshold potential
1075:Diagram at nih.gov
711:Muscle & Nerve
471:Stuart et al. 1997
372:Use of medications
259:membrane potential
127:Alan Lloyd Hodgkin
52:membrane potential
40:
1095:Action potentials
1090:Electrophysiology
1053:Nosek, Thomas M.
783:(11): 1392–1406.
242:Hyperpolarization
143:excitable tissues
137:. Through use of
44:electrophysiology
1102:
1066:
1061:. Archived from
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992:
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948:
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754:(9): 1575–1585.
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602:Wang et al. 2011
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342:ALS and diabetes
310:Febrile seizures
123:action potential
60:action potential
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577:, p. 1581.
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548:, p. 1576.
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316:febrile seizure
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58:to initiate an
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1065:on 2016-03-24.
1048:
1047:External links
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1011:Brain Research
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993:
967:(3): 125–131.
949:
944:978-0781744898
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902:(3): 207–219.
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862:(4): 357–377.
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820:(4): 289–295.
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717:(2): 137–158.
704:
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685:
683:, p. 213.
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643:, p. 291.
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589:, p. 150.
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565:, p. 141.
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536:, p. 138.
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524:, p. 137.
514:
512:, p. 281.
510:Trautwein 1963
502:
500:, p. 144.
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485:, p. 330.
483:Trautwein 1963
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473:, p. 127.
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115:Walther Nernst
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661:. Retrieved
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430:Rushton 1927
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393:Role of diet
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368:may result.
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203:ion channels
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64:neuroscience
47:
41:
31:
23:
378:QT interval
327:patch clamp
56:depolarized
1084:Categories
1017:: 87–102.
703:References
389:, or TdP.
232:Variations
172:entails a
161:See also:
366:arrythmia
359:Arrythmia
174:summation
109:Discovery
91:potassium
1031:21907327
916:19937318
886:16993895
834:22064575
805:22207608
797:20946278
768:32160313
352:diabetes
331:in vitro
296:ischemia
266:sheath.
99:chloride
54:must be
1039:8431090
981:9061867
924:6003098
877:1514939
739:2914214
731:9466589
196:of the
74:(PNS).
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350:and
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101:can
89:and
1019:doi
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