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Afterhyperpolarization

Afterhyperpolarization (AHP) is a hyperpolarizing phase that occurs immediately following the repolarization of an action potential in neurons, during which the membrane potential becomes more negative than the resting potential, typically due to the activation of potassium (K⁺) channels that allow an efflux of K⁺ ions.^[1] This phenomenon serves as a key regulatory mechanism in neuronal excitability, limiting the frequency of action potentials and contributing to the refractory period.^[2] AHP is observed across various neuron types, including pyramidal cells in the hippocampus and cortex, and is essential for controlling spike timing and firing patterns in central nervous system circuits.^[3] AHP can be classified into three main types based on their duration and underlying ionic mechanisms: the fast AHP (fAHP), which lasts milliseconds and is primarily mediated by voltage-gated or calcium-activated large-conductance (BK) K⁺ channels; the medium AHP (mAHP), enduring hundreds of milliseconds and involving small-conductance (SK) Ca²⁺-activated K⁺ channels; and the slow AHP (sAHP), which persists for seconds and is a Ca²⁺-dependent process linked to apamin-insensitive K⁺ conductances, such as KCNQ channels in certain pyramidal neurons, often triggered by bulk cytoplasmic calcium levels.^[4] These components arise from calcium influx during the action potential, which activates downstream signaling involving neuronal calcium sensors like hippocalcin and modulation of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P₂) levels to gate K⁺ conductances.^[4] The molecular identity of sAHP channels remains partially debated, with evidence supporting roles for KCNQ5 in certain pyramidal neurons but not universal BK or SK involvement.^[4] More recent studies have identified intermediate-conductance Ca²⁺-activated K⁺ (IKCa; KCa3.1) channels as a primary mediator of sAHP in hippocampal CA1 pyramidal neurons.^[5] Physiologically, AHP plays a critical role in spike-frequency adaptation, where prolonged or repetitive firing leads to cumulative hyperpolarization that reduces subsequent excitability, thereby shaping dynamic firing ranges and preventing excessive network activity.^[3] In hippocampal CA1 pyramidal cells, for instance, sAHP underlies learning-related plasticity by modulating postburst hyperpolarizations, influencing processes like memory consolidation.^[6] Additionally, AHP contributes to olfactory coding in mitral cells by regulating inter-spike intervals and adaptation to sensory inputs, with its amplitude modifiable by experience.^[3] Disruptions in AHP mechanisms have been implicated in neurological disorders, such as epilepsy, where reduced sAHP can enhance hyperexcitability.^[4] First described in the early 1980s in studies of hippocampal neurons, AHP research continues to elucidate its neuromodulatory targets and therapeutic potential.^[4]

Fundamentals

Definition

Afterhyperpolarization (AHP), also known as the undershoot, is the phase of a neuron's action potential in which the membrane potential transiently becomes more negative than the resting potential immediately after repolarization.^[7] This hyperpolarization occurs as the membrane potential falls below the typical resting value of around -70 mV, often reaching -80 mV or lower, before gradually returning to baseline.^[8] The phenomenon arises directly following the closure of voltage-gated sodium channels and the continued activity of potassium channels during the repolarization phase.^[7] Biophysically, the AHP is characterized by durations ranging from 10 to 100 ms in its initial phases, distinguishing it from longer-lasting components that can extend to seconds.^[9] It is primarily driven by an increase in potassium conductance, which allows excess potassium ions to efflux from the neuron, making the interior more negative relative to the extracellular space.^[7] This transient hyperpolarization contrasts with the steady resting membrane potential, which is maintained by the ongoing activity of the sodium-potassium ATPase pump that actively transports ions to counteract passive leaks.^[7]

Relation to Action Potential Phases

The action potential in neurons follows a characteristic sequence of phases that restore the membrane potential after excitation. Depolarization begins when voltage-gated sodium channels open, allowing Na⁺ influx that rapidly shifts the membrane potential from the resting level toward the sodium equilibrium potential (around +60 mV). This is followed by repolarization, where voltage-gated potassium channels activate more slowly, permitting K⁺ efflux that drives the potential back toward the potassium equilibrium potential (E_K ≈ -90 mV). Afterhyperpolarization (AHP) then occurs as repolarization overshoots the resting potential, with the membrane hyperpolarizing further due to the lingering openness of these K⁺ channels before they fully deactivate.^[10]^[7] This phase precedes the gradual return to the baseline resting membrane potential (approximately -70 mV), which is primarily determined by the high permeability to K⁺ ions at rest.^[11] Temporally, AHP peaks shortly after the action potential spike, typically within 1-5 ms, reflecting the brief delay in K⁺ channel closure following repolarization. Its amplitude varies but commonly ranges from -5 to -20 mV below the resting potential, resulting in membrane voltages of -75 to -90 mV or more negative, approaching E_K. The magnitude and duration of AHP are influenced by the height and duration of the preceding spike, as taller or longer spikes enhance K⁺ channel activation (via greater depolarization) and associated calcium influx, amplifying the hyperpolarizing K⁺ current.^[12]^[7] By extending the period of membrane hyperpolarization, AHP contributes to the refractory period, particularly the relative refractory phase, during which a stronger-than-normal stimulus is required to initiate another action potential due to the distance from threshold. This mechanism limits immediate re-excitation, ensuring unidirectional propagation and controlling firing rates, while the absolute refractory period (spanning depolarization and early repolarization) is primarily governed by sodium channel inactivation.^[2]^[10]

Physiological Mechanisms

Ionic Currents Involved

The afterhyperpolarization (AHP) following an action potential is primarily driven by outward potassium currents that hyperpolarize the membrane below its resting potential. Two key ionic currents contribute to this phase: voltage-gated delayed rectifier potassium currents (I_{K,dr}) and calcium-activated potassium currents (I_{K,Ca}). The I_{K,dr} arises from channels that activate during depolarization and remain open during the repolarization phase, allowing sustained K^+ efflux even after the action potential peak.^[2] This efflux is augmented by residual activation from the preceding spike, contributing particularly to the fast component of the AHP in various central neurons.^[13] In parallel, I_{K,Ca} is activated by elevated intracellular Ca^{2+} levels resulting from voltage-gated Ca^{2+} influx during the action potential. These channels, often of the small-conductance (SK) type, bind Ca^{2+} with cooperative kinetics, typically exhibiting a Hill coefficient of 2-4, which enables rapid activation in response to micromolar Ca^{2+} concentrations.^[14] The activation of I_{K,Ca} further enhances K^+ efflux, prolonging the hyperpolarization and distinguishing it from purely voltage-dependent mechanisms.^[15] The membrane potential (V_m) during the AHP can be approximated using the Goldman-Hodgkin-Katz (GHK) equation, which accounts for the elevated potassium permeability (P_K) dominating over sodium (P_{Na}) and chloride (P_{Cl}) permeabilities:

V_m \approx \frac{RT}{F} \ln \left( \frac{P_K [K^+]_o + P_{Na} [Na^+]_o + P_{Cl} [Cl^-]_i}{P_K [K^+]_i + P_{Na} [Na^+]_i + P_{Cl} [Cl^-]_o} \right)

This formulation highlights how increased P_K drives V_m toward the K^+ equilibrium potential, typically around -80 to -90 mV, underscoring the efflux-driven hyperpolarization.^[16] The temporal dynamics of these currents are characterized by distinct time constants. For I_{K,dr}, deactivation occurs with a time constant (τ) of approximately 10-50 ms, allowing a transient but significant contribution to the initial AHP decay.^[17] In contrast, I_{K,Ca} activation is faster, with τ values around 5-15 ms upon Ca^{2+} binding, though its decay depends on Ca^{2+} clearance and can extend the AHP over tens to hundreds of milliseconds.^[18] These kinetics ensure that the AHP effectively bridges the action potential phases by modulating ion fluxes post-repolarization.

Molecular and Cellular Components

Afterhyperpolarization (AHP) in neurons is primarily mediated by specific potassium channel families that respond to changes in intracellular calcium and voltage. The fast AHP component involves big-conductance calcium-activated potassium (BK) channels, encoded by the KCNMA1 gene, which exhibit high single-channel conductance (100-300 pS) and are directly gated by both voltage and calcium, facilitating rapid repolarization following action potentials. Small-conductance calcium-activated potassium (SK) channels, comprising subtypes SK1-3 (KCNN1-3 genes), with lower conductance (4-14 pS), contribute to the medium AHP through their sensitivity to submicromolar calcium levels via constitutive binding to calmodulin. Intermediate-conductance calcium-activated potassium (IK) channels, primarily KCa3.1 (KCNN4 gene), with conductance around 25-80 pS, are implicated in the slow AHP in certain neuronal populations, such as hippocampal CA1 pyramidal cells. Additionally, voltage-gated delayed rectifier Kv channels, including subtypes like Kv1.1 (KCNA1) and Kv1.6 (KCNA6), support the AHP by providing sustained outward potassium currents that prolong hyperpolarization after repolarization, particularly in axonal and somatic regions. KCNQ channels (Kv7 family, e.g., KCNQ5) have also been proposed to contribute to the slow AHP in some pyramidal neurons through modulation by phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P₂) levels.^[19] The subcellular localization of these channels varies across neuron types, influencing the spatial control of AHP. In hippocampal pyramidal neurons, SK channels, especially SK2, are prominently expressed in both somatic and dendritic compartments, with a polarized distribution that increases toward distal dendrites, enabling localized regulation of excitability during synaptic integration. BK channels are often clustered at spike initiation zones, such as the axon initial segment, to sharpen action potential waveforms, while IK channels show somatic enrichment in cortical interneurons. Kv1 family channels, like Kv1.1 and Kv1.6, are typically localized to juxtaparanodal regions of axons in myelinated neurons, contributing to the maintenance of hyperpolarized states post-firing. Regulation of AHP channels involves intricate molecular interactions that fine-tune their activity. Calcium buffering by proteins such as calbindin-D28k modulates AHP amplitude by limiting local calcium rises near channel pores, thereby reducing SK and BK activation in buffered compartments like dendrites. Phosphorylation by protein kinase A (PKA) inhibits SK channel activity through sites in the calmodulin-binding domain, decreasing calcium sensitivity and shortening the medium AHP, while Ca2+/calmodulin-dependent protein kinase II (CaMKII) phosphorylates BK channels at sites like Thr107 on the Slo subunit, enhancing conductance and prolonging the fast AHP. The molecular basis of the slow AHP (sAHP) remains incompletely understood, with debate centering on the involvement of Na+/K+-ATPase pumps alongside IK channels and KCNQ channels; neuronal calcium sensors such as hippocalcin link bulk cytoplasmic calcium increases to sAHP activation, often through downstream signaling involving PtdIns(4,5)P₂; some evidence supports a pump-mediated hyperpolarization driven by sodium accumulation during repetitive firing, though Ca2+-activated K+ currents predominate in many models.^[20]

Types and Characteristics

Fast Afterhyperpolarization

The fast afterhyperpolarization (fAHP) is a brief hyperpolarizing phase immediately following repolarization of a single action potential in neurons, characterized by a duration of 5–20 ms and a hyperpolarization typically of several millivolts below the resting potential.^[21] This rapid event is primarily mediated by the activation of large-conductance calcium-activated potassium (BK) channels, which open in response to calcium influx during the action potential, alongside contributions from voltage-gated potassium channels that facilitate quick membrane repolarization.^[22] Unlike slower afterhyperpolarizations, the fAHP is a voltage- and calcium-driven process tightly coupled to individual spikes, decaying rapidly without significant accumulation over multiple firings.^[21] The fAHP is prominent in central neurons, including cortical pyramidal cells such as those in the CA1 region of the hippocampus, where it helps enforce limits on high-frequency firing by hyperpolarizing the membrane and reducing excitability for subsequent spikes.^[22] In these cells, the fAHP enables initial burst-like activity above 100 Hz but promotes early spike frequency adaptation, preventing sustained high rates that could lead to excessive depolarization or channel inactivation.^[23] Similarly, in cerebellar Purkinje neurons, the fAHP maintains tonic single-spike firing patterns, counteracting potential afterdepolarizations that might trigger bursts.^[24] Experimental evidence for the fAHP's properties comes from patch-clamp recordings, which demonstrate its fast onset—often within 100 µs after calcium entry—directly following the action potential undershoot.^[21] Application of iberiotoxin, a selective BK channel blocker at concentrations of 100–200 nM, abolishes the fAHP in these neurons, resulting in slowed spike repolarization, elevated thresholds, and altered firing dynamics, such as reduced initial frequencies in pyramidal cells or induced bursting in Purkinje cells.^[22] These observations, obtained under whole-cell voltage- or current-clamp conditions at physiological temperatures, confirm the BK channels' dominant role in shaping this rapid phase.^[23]

Medium and Slow Afterhyperpolarizations

The medium afterhyperpolarization (mAHP) is a calcium-dependent hyperpolarizing event that follows action potentials in various central neurons, lasting typically 100-300 ms and peaking around 200 ms post-spike.^[18] It is activated by calcium influx from a single action potential or a brief burst of spikes, contributing to spike frequency adaptation by limiting rapid repetitive firing.^[25] In cortical pyramidal neurons, the mAHP is primarily mediated by small-conductance calcium-activated potassium (SK) channels, particularly SK2 and SK3 subtypes, which are highly sensitive to the blocker apamin, reducing mAHP amplitude when applied.^[25] Additional contributions to mAHP come from hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and M-type potassium (Kv7/KCNQ) channels in regions like the hippocampus, where these voltage-dependent mechanisms stabilize excitability at different membrane potentials.^[18] Unlike the brief, voltage-gated fast AHP, the mAHP exhibits frequency dependence, with its amplitude increasing during repetitive spiking to promote adaptation.^[18] The slow afterhyperpolarization (sAHP), in contrast, is a prolonged hyperpolarization enduring 1-30 seconds and peaking on the timescale of seconds, requiring sustained trains of action potentials (typically 20-150 spikes at 50 Hz) for full activation in hippocampal CA1 pyramidal neurons.^[26] This form is prominent in hippocampal and autonomic neurons, where it regulates long-term excitability and spike accommodation following intense activity.^[27] Its mechanisms remain debated, involving a calcium-dependent potassium current mediated by intermediate-conductance channels like KCa3.1 (IK), potentially in hybrid with SK or AP-1 pathways, alongside contributions from the Na+/K+-ATPase pump that overlaps in the later phases.^[27] The sAHP is apamin-insensitive, distinguishing it from SK-dominated processes, and its amplitude builds cumulatively with firing frequency, though less steeply than the mAHP.^[26] Key distinctions between mAHP and sAHP lie in their temporal profiles and activation thresholds: the mAHP responds to isolated spikes with a sub-second decay, while the sAHP demands repetitive input and persists for seconds to regulate broader firing patterns.^[18] Both exhibit frequency dependence, accumulating during trains unlike the fast AHP, but the sAHP's longer duration enables sustained inhibition critical for network stability in regions like the hippocampus.^[27]

Functional Roles

Regulation of Firing Patterns

Afterhyperpolarization (AHP) serves as a critical feedback mechanism that hyperpolarizes the neuronal membrane following an action potential, thereby elevating the threshold for subsequent spikes and enforcing minimal inter-spike intervals (ISIs). This hyperpolarization, primarily driven by calcium-activated potassium currents, delays the membrane's return to resting potential, limiting the immediacy of depolarization and thus controlling the overall discharge rate. In regularly firing neurons, the duration and amplitude of the AHP directly determine the refractory period, with longer or deeper AHPs resulting in prolonged ISIs and reduced maximum firing frequencies.^[3] The fast AHP (fAHP), typically lasting less than 25 ms and mediated by large-conductance BK channels, particularly restricts high-frequency bursting by curtailing intra-burst spike rates, preventing excessive excitability during repetitive discharges. In contrast, the slow AHP (sAHP), which persists for seconds and involves apamin-insensitive Ca²⁺-dependent K⁺ channels such as KCNQ channels, promotes spike-frequency adaptation by accumulating over multiple spikes, gradually decreasing firing rates during sustained input and stabilizing neuronal output against overstimulation. These components collectively shape firing patterns, with the fAHP enforcing short-term limits on burst duration and the sAHP inducing longer-term reductions in excitability.^[4]^[2] In spinal motoneurons, the AHP prominently sets the steady-state firing frequency during voluntary contractions, typically ranging from 10 to 50 Hz, where shorter AHP durations (e.g., 20-50 ms) in fast-twitch motor units enable higher rates compared to longer AHPs (50-100 ms) in slow-twitch units. Seminal studies demonstrate that the minimal repetitive firing rate is inversely related to AHP duration, with the maximum frequency approximating the reciprocal of the AHP time course. For instance, doubling the AHP duration can halve the achievable firing rate, underscoring its role in matching motor output to muscle fiber properties.^[28]^[29] In thalamic relay neurons, AHP depth modulates burst firing propensity, with deeper hyperpolarizations deinactivating T-type calcium channels to facilitate rebound bursts upon depolarization, while shallower AHPs favor tonic firing. This regulation influences burst characteristics, such as spike number within a burst (e.g., 1-5 spikes) and latency (e.g., 50-150 ms), thereby controlling the transition between burst and single-spike modes critical for sensory relay. Overall, neuronal firing rates exhibit an inverse proportionality to AHP amplitude, where enhancements in AHP strength can reduce rates by 20-50% in sustained activity, highlighting its precise control over discharge timing.^[30]^[31]

Influence on Neural Oscillations and Adaptation

The slow afterhyperpolarization (sAHP) contributes to the generation of theta rhythms (4-8 Hz) in the hippocampus by regulating neuronal excitability, with its suppression by cholinergic inputs from the medial septum being essential for facilitating these oscillations during exploratory behavior and memory processing.^[32] Cholinergic activation reduces the sAHP amplitude, allowing for sustained depolarizations and rhythmic firing patterns that align with theta frequency, thereby enhancing the synchronization of hippocampal networks.^[33] This modulation ensures that theta rhythms can effectively coordinate information flow, supporting functions such as spatial navigation. In the entorhinal cortex, the afterhyperpolarization (AHP) interacts with hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in layer II stellate cells to generate subthreshold membrane oscillations in the theta range.^[34] During the AHP following action potentials, HCN channels activate, providing a rebound excitation that, in concert with persistent sodium currents, drives resonant oscillations essential for the periodic firing of grid cells.^[35] These oscillations underpin the spatial scaling and stability of grid patterns, which are critical for path integration and spatial memory formation in the hippocampal-entorhinal system.01135-4) The sAHP underlies spike-frequency adaptation by accumulating during repetitive firing, leading to progressive hyperpolarization that reduces neuronal excitability and firing rates over sustained stimulus trains.^[36] This adaptation mechanism is implicated in habituation, where repeated stimuli elicit diminishing responses, as the medium and slow AHP currents influence interspike intervals and promote response decrement in sensory and motor circuits.^[37] In the medial temporal lobe, AHP dynamics modulate the encoding of episodic memories by controlling the temporal precision and burst timing of pyramidal neurons, enabling the binding of multisensory elements into coherent representations.^[38] Alterations in AHP, particularly an enlarged sAHP, occur in aging-related cognitive decline, impairing synaptic integration and reducing the efficacy of memory encoding processes in hippocampal and entorhinal regions.^[38]

Experimental and Clinical Aspects

Measurement and Modulation Techniques

Afterhyperpolarization (AHP) in neurons is primarily measured using intracellular recording techniques that allow direct assessment of membrane potential changes following action potentials. Whole-cell patch-clamp electrophysiology in current-clamp mode is a standard method, where neurons are stimulated with depolarizing current pulses to evoke single spikes or trains, enabling quantification of AHP amplitude (typically the peak hyperpolarization below resting potential) and duration (time to return to baseline). For example, in hippocampal CA1 pyramidal neurons, the fast AHP (fAHP) is elicited by brief (1-2 ms) current injections to trigger action potentials, while medium (mAHP) and slow (sAHP) components are assessed after repetitive firing protocols, such as 25 pulses at 50 Hz. Sharp electrode recordings, using high-resistance (50-100 MΩ) intracellular electrodes filled with potassium-based solutions, provide an alternative for stable long-term measurements in brain slices, particularly useful for avoiding dialysis effects in smaller neurons. Pharmacological modulation of AHP relies on blockers targeting the underlying calcium-activated potassium channels to isolate specific components. Apamin, a selective inhibitor of small-conductance (SK) channels, is commonly applied (10-100 nM) to suppress mAHP, revealing its contributions to spike frequency adaptation by increasing neuronal excitability and reducing post-train hyperpolarization; sAHP is typically apamin-insensitive.^[39]^[4] For fAHP, mediated by large-conductance (BK) channels, iberiotoxin (50-100 nM) or tetraethylammonium (TEA, 1-10 mM) effectively blocks the rapid hyperpolarizing phase, allowing assessment of its role in action potential repolarization and refractory periods. These agents are bath-applied during patch-clamp recordings to compare AHP waveforms before and after perfusion, ensuring specificity through voltage-clamp confirmation of current blockade.^[40] Optogenetic approaches enable precise spatiotemporal control of intracellular calcium to modulate AHP, as its activation depends on spike-evoked Ca²⁺ influx. This technique is particularly valuable in brain slices or in vivo for targeted manipulation without pharmacological diffusion issues, allowing correlation of AHP changes with firing patterns via simultaneous electrophysiology. In vivo measurement of AHP is challenging due to limited intracellular access, so extracellular multi-electrode arrays (MEAs) are employed to infer AHP properties from population-level spike timing. High-density silicon probes (e.g., 64-128 channels) record extracellular action potentials, where AHP strength is estimated from inter-spike interval (ISI) distributions and variability; stronger AHPs prolong ISIs and reduce firing rates during sustained activity. For instance, in suprachiasmatic nucleus recordings, diurnal variations in AHP duration correlate with firing rates, with shorter AHP associated with higher daytime activity.^[31] Computational modeling complements experimental techniques by simulating AHP dynamics in realistic neuronal geometries. The NEURON software environment is widely used to incorporate Hodgkin-Huxley-type models of Ca²⁺-activated K⁺ conductances, allowing simulation of current-clamp protocols to predict AHP amplitude under varying ionic conditions or channel densities.^[2] These models validate experimental data, such as how fAHP conductance paradoxically enhances gain in regularly firing neurons, by tuning parameters to match measured ISI statistics.^[2]

Pathophysiological Relevance

Alterations in afterhyperpolarization (AHP) mechanisms contribute to neuronal hyperexcitability in epilepsy, particularly in cases involving hippocampal sclerosis, where reduced slow AHP (sAHP) in pyramidal neurons diminishes post-burst hyperpolarization, thereby promoting burst firing and seizure susceptibility.^[41] In temporal lobe epilepsy with hippocampal sclerosis, acute epileptic activity induces phosphorylation-dependent suppression of the sAHP via protein kinase A-mediated downregulation of KCa3.1 channels, exacerbating network hyperexcitability.^[42]^[43] In Alzheimer's disease, enhancement of the sAHP in hippocampal CA1 pyramidal neurons reduces neuronal excitability and impairs synaptic plasticity, contributing to memory deficits observed in both aging and disease models.^[44] This sAHP amplification correlates with learning impairments, as increased calcium influx through L-type channels during aging and amyloid-beta pathology strengthens the underlying potassium currents.^[45] Mutations in calcium-activated potassium (KCa) channels, such as loss-of-function variants in the large-conductance BK channel (KCNMA1), disrupt mitochondrial function and Purkinje cell excitability, leading to progressive cerebellar ataxia in both human patients and mouse models.^[46] Similarly, episodic ataxia type 2 involves dysregulated KCa signaling downstream of P/Q-type calcium channel mutations, resulting in impaired neuronal repolarization and motor coordination deficits.^[47] Recent post-2020 findings highlight AHP dysregulation in autism spectrum disorders through variants in the SK2 channel gene (KCNN2), which cause dominant neurodevelopmental syndromes featuring intellectual disability, motor delays, and autistic features by altering medium AHP and synaptic transmission.^[48]^[49] Therapeutically, SK channel activators like NS309 reduce epileptiform activity in hippocampal slices from epileptic models by enhancing sAHP and suppressing burst firing, offering potential for seizure control.^[50] In Parkinson's disease, modulation of the slow AHP current (IsAHP) in striatal cholinergic interneurons restores pause responses and regularizes firing patterns disrupted by dopamine depletion, suggesting AHP-targeted interventions to alleviate motor symptoms.^[51] Activating KCa channels, including SK and BK subtypes, also improves Purkinje neuron spiking in spinocerebellar ataxia models, indicating broader therapeutic potential for ataxias.^[52]

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Biophysical alterations of hippocampal pyramidal neurons in ...
Our studies have demonstrated that calcium-activated potassium currents that mediate the slow post-burst afterhyperpolarization (AHP) are reduced after learning ...
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Slow Afterhyperpolarization - an overview | ScienceDirect Topics
Slow afterhyperpolarization is a prolonged, calcium-dependent, potassium current lasting seconds after an action potential, linked to neuronal excitability.
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Loss-of-function BK channel mutation causes impaired mitochondria ...
Mar 4, 2020 · These studies indicate that a loss-of-function BK channel mutation causes ataxia and acts by reducing mitochondrial and subsequently cellular viability.
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KCa Channels as Therapeutic Targets in Episodic Ataxia Type-2
Episodic ataxia type-2 (EA2) is a rare neurological disorder caused by mutations in the gene encoding the Cav2.1α1 subunit of the P/Q-type voltage-dependent ...
[46]
Variants in the SK2 channel gene (KCNN2) lead to ... - PubMed
Dec 1, 2020 · Patients with KCNN2 variants had motor and language developmental delay, intellectual disability often associated with early-onset movement disorders.
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Variants in the SK2 channel gene ( KCNN2 ) lead to dominant ...
Recently, point mutations in KCNN2 have been described to result in a spectrum of neurodevelopmental movement disorders (Mochel et al., 2020) .
[48]
Altered expression and function of small-conductance (SK) Ca2+- ...
In order to test this possibility, we tested whether the selective SK channel opener NS309 would decrease the epileptiform activity in the hippocampus of ...
[49]
Reduction of an Afterhyperpolarization Current Increases Excitability ...
Apr 27, 2011 · Moreover, it has been postulated that the loss of the pause response in Parkinson's disease is related to a diminution of IsAHP, a slow outward ...
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Targeting potassium channels to treat cerebellar ataxia - PMC
Mutations in potassium channel kcnd3 cause spinocerebellar ataxia type 19. ... KCa channels as therapeutic targets in episodic ataxia type‐2. J Neurosci ...