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Calcium-dependent current generating the afterhyperpolarization of hippocampal neurons
Abstract
A single-electrode voltage-clamp technique was employed on in vitro hippocampal slices to examine the membrane current responsible for the slow afterhyperpolarization (AHP) in CA1 pyramidal cells. This was achieved by using conventional procedures to evoke an AHP in current clamp, followed rapidly by a switch into voltage clamp (hybrid clamp). The AHP current showed a dependence on extracellular K+, which was close to that predicted for a K+ current by the Nernst equation. The AHP current could be blocked by Cd2+ or norepinephrine. Although the AHP current showed a requirement for voltage-dependent Ca2+ entry, the current did not show any clear intrinsic voltage dependence. Once activated, AHP current is not turned off by hyperpolarizing the membrane potential. The effects of norepinephrine, Cd2+, and tetraethylammonium (TEA) were used to identify an AHP current component to the outward current evoked by depolarizing voltage commands from holding potentials that approximate to the resting potential for these cells. The AHP current can contribute significantly to the outward current during the depolarizing command. Upon repolarization it is evident as a slow outward tail current. This slow tail current had the same time constant as AHP currents evoked by hybrid clamp. Fast components to the tail currents were also observed. These were sensitive to Cd2+ and TEA. They probably represent a voltage-sensitive gKCa, sometimes termed C-current. The strong sensitivity to voltage and TEA displayed by the conventionally described gKCa (IC) are properties inconsistent with the AHP. It seems likely that the AHP current (IAHP) represents a Ca2+-activated K+ current separate from IC and that these two currents coexist in the same cell.
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“AHP currents are mainly mediated by calcium-dependent potassium channels [77, 78], but also partly by calcium-independent potassium channels [79].”
From Chronic unpredictable stress induces depression-related behaviors by suppressing AgRP neuron activity (2021) · cites this paper as [77]
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“To analyze AHP currents in a more controlled and quantitative manner, we used the hybrid clamp method (Lancaster and Adams, 1986; Wolfart et al., 2001).”
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“Voltage-clamp studies have revealed that the current, sIAHP, underlying the sAHP reaches its maximum with a time constant of several hundred milliseconds and decays with a time constant of>1s, and the kinetics of the current are temperature dependent [5, 6].”
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“After brief Ca2+ influx or bursts of action potentials this current displays a distinct slow, rising phase followed by an even slower decay (Lancaster & Adams, 1986).”
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“(2) The AHP following a single action potential was relatively small (Lancaster and Adams 1986).”
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“…currents should lead to higher intracellular Ca2+ activity, providing the mechanism to activate the large (KCa1 or BKCa) and small (KCa2 or SKCa) conductance Ca 2+-activated K+ (KCa) channels that initiate repolarization and the ensuing afterhyperpolarization (Lancaster and Adams 1986; Storm 1987).”
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“MODELING SPIKE-BASED AFTER-HYPERPOLARIZATION CURRENTS Since fluctuations in somatic calcium concentrations strongly match the timing of action potentials, and AHP currents are predominantly carried by calcium-dependent potassium channels (Lancaster and Adams, 1986; Prakriya et al., 1996; Abel et al., 2004; Lee et al.,…”
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Disterhoft, J. F., Coulter, D. A., & Alkon, D. L. (1988) · Springer eBooks · doi:10.1007/978-1-4757-9610-0_10 · Cited by 15
Palma, J., Massimiliano Versace, A., & Grossberg, S. (2011) · Journal of Computational Neuroscience · doi:10.1007/s10827-011-0354-8 · Cited by 14
“AHP currents AHP currents are predominantly calciumdependent potassium currents (Hotson and Prince 1980; Lancaster and Adams 1986), but also partly calciumindependent voltage potassium currents (Lorenzon and Foehring 1992).”
BackgroundInfluential
Metadata
- Authors
- Lancaster, B., & Adams, P. R.
- ORCID
- Adams, P. R.
- Venue
- Journal of Neurophysiology
- Publisher
- American Physiological Society
- Published
- 1986-06-01
- Volume
- 55
- Issue
- 6
- Pages
- 1268-1282
- ISSN
- 0022-3077 (ISSN-L)
- 1522-1598
- OpenAlex
- W1876408798
- Cited by
- 547
- References
- 0
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2023: 4 · 2022: 2 · 2021: 5 · 2020: 4 · 2019: 8 · 2018: 6 · 2017: 5 · 2016: 4 · 2015: 3 · 2014: 1 · 2013: 7 · 2012: 11
- FWCI
- 9.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurophysiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS18579)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- afterhyperpolarization, calcium-activated potassium current, CA1 pyramidal neurons, tetraethylammonium sensitivity, cadmium block, norepinephrine, voltage-gated potassium channels
- MeSH terms
- Action Potentials, Animals, Calcium, Hippocampus, Ion Channels, Kinetics, Neural Conduction, Synaptic Transmission, Potassium, Rats, In Vitro Techniques
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