Learning-Induced Reversal of the Effect of Noradrenalin on the Postburst AHP

2006 ◽  
Vol 96 (4) ◽  
pp. 1728-1733 ◽  
Author(s):  
Inbar Brosh ◽  
Kobi Rosenblum ◽  
Edi Barkai
Keyword(s):  
Potassium Current ◽  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Piriform Cortex ◽  
Sk Channels ◽  
Similar Extent ◽  
Protein Expression Level ◽  
Calcium Dependent ◽  
The Difference ◽  
Small Conductance

Pyramidal neurons in the piriform cortex from olfactory-discrimination–trained rats have reduced postburst afterhyperpolarization (AHP), for 3 days after learning, and are thus more excitable during this period. Such AHP reduction is caused by decreased conductance of one or more of the calcium-dependent potassium currents, IAHP and s IAHP, that mediate the medium and slow AHPs. In this study, we examined which potassium current is reduced by learning and how the effect of noradrenalin (NE) on neuronal excitability is modified by such reduction. The small conductance (SK) channels inhibitor, apamin, that selectively blocks IAHP, reduced the AHP in neurons from trained, naïve, and pseudotrained rats to a similar extent, thus maintaining the difference in AHP amplitude between neurons from trained rats and controls. In addition, the protein expression level of the SK1, SK2, and SK3 channels was also similar in all groups. NE, which was shown to enhance IAHP while suppressing S IAHP, reduced the AHP in neurons from controls but enhanced the AHP in neurons from trained rats. Our data show that learning-induced enhancement of neuronal excitability is not the result of reduction in the IAHP current. Thus it is probably mediated by reduction in conductance of the other calcium-dependent potassium current, s IAHP. Consequently, the effect of NE on neuronal excitability is reversed. We propose that the change in the effect of NE after learning may act to counterbalance learning-induced hyperexcitability and preserve the piriform cortex ability to subserve olfactory learning.

scholarly journals Small-conductance Ca2+-activated K+ channels modulate action potential-induced Ca2+ transients in hippocampal neurons

2013 ◽  
Vol 109 (6) ◽  
pp. 1514-1524 ◽  
Author(s):  
Raffaella Tonini ◽  
Teresa Ferraro ◽  
Marisol Sampedro-Castañeda ◽  
Anna Cavaccini ◽  
Martin Stocker ◽  
...  
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Apical Dendrite ◽  
Channel Blockers ◽  
Sk Channels ◽  
Hippocampal Pyramidal Neurons ◽  
Voltage Gated ◽  
Small Conductance

In hippocampal pyramidal neurons, voltage-gated Ca2+ channels open in response to action potentials. This results in elevations in the intracellular concentration of Ca2+ that are maximal in the proximal apical dendrites and decrease rapidly with distance from the soma. The control of these action potential-evoked Ca2+ elevations is critical for the regulation of hippocampal neuronal activity. As part of Ca2+ signaling microdomains, small-conductance Ca2+-activated K+ (SK) channels have been shown to modulate the amplitude and duration of intracellular Ca2+ signals by feedback regulation of synaptically activated Ca2+ sources in small distal dendrites and dendritic spines, thus affecting synaptic plasticity in the hippocampus. In this study, we investigated the effect of the activation of SK channels on Ca2+ transients specifically induced by action potentials in the proximal processes of hippocampal pyramidal neurons. Our results, obtained by using selective SK channel blockers and enhancers, show that SK channels act in a feedback loop, in which their activation by Ca2+ entering mainly through L-type voltage-gated Ca2+ channels leads to a reduction in the subsequent dendritic influx of Ca2+. This underscores a new role of SK channels in the proximal apical dendrite of hippocampal pyramidal neurons.

Impaired Cl− Extrusion in Layer V Pyramidal Neurons of Chronically Injured Epileptogenic Neocortex

2005 ◽  
Vol 93 (4) ◽  
pp. 2117-2126 ◽  
Author(s):  
Xiaoming Jin ◽  
John R. Huguenard ◽  
David A. Prince
Keyword(s):  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Gabaergic Inhibition ◽  
Adult Rats ◽  
Positive Shift ◽  
Mature Brain ◽  
Significant Difference ◽  
The Difference ◽  
Layer V ◽  
Patch Technique

In the mature brain, the K+/Cl− cotransporter KCC2 is important in maintaining low [Cl−]i, resulting in hyperpolarizing GABA responses. Decreases in KCC2 after neuronal injuries result in increases in [Cl−]i and enhanced neuronal excitability due to depolarizing GABA responses. We used the gramicidin perforated-patch technique to measure ECl (∼ EGABA) in layer V pyramidal neurons in slices of partially isolated sensorimotor cortex of adult rats to explore the potential functional consequence of KCC2 downregulation in chronically injured cortex. EGABA was measured by recording currents evoked with brief GABA puffs at various membrane potentials. There was no significant difference in ECl between neurons in control and undercut animals (–71.2 ± 2.6 and –71.8 ± 2.8 mV, respectively). However, when loaded with Cl− by applying muscimol puffs at 0.2 Hz for 60 s, neurons in the undercut cortex had a significantly shorter time constant for the positive shift in ECl during the Cl− loading phase (4.3 ± 0.5 s for control and 2.2 ± 0.4 s for undercut, P < 0.01). The positive shift in ECl 3 s after the beginning of Cl− loading was also significantly larger in the undercut group than in the control, indicating that neurons in undercut cortex were less effective in maintaining low [Cl−]i during repetitive activation of GABAA receptors. Application of furosemide eliminated the difference between the control and undercut groups for both of these measures of [Cl−]i regulation. The results suggest an impairment in Cl− extrusion resulting from decreased KCC2 expression that may reduce the strength of GABAergic inhibition and contribute to epileptogenesis.

scholarly journals Intrinsic Excitability Increase in Cerebellar Purkinje Cells Following Delay Eyeblink Conditioning in Mice

2018 ◽  
Author(s):  
Heather K. Titley ◽  
Gabrielle V. Watkins ◽  
Carmen Lin ◽  
Craig Weiss ◽  
Michael McCarthy ◽  
...  
Keyword(s):  
Purkinje Cells ◽  
Neuronal Excitability ◽  
Eyeblink Conditioning ◽  
Underlying Mechanism ◽  
Learning Task ◽  
Sk Channels ◽  
Calcium Dependent ◽  
Cerebellar Learning ◽  
Intrinsic Plasticity ◽  
Cerebellar Purkinje Cells

AbstractCerebellar learning is canonically thought to rely on synaptic plasticity, particularly at synaptic inputs to Purkinje cells. Recently, however, other complementary mechanisms have been identified. Intrinsic plasticity is one such mechanism, and depends in part on the down-regulation of calcium-dependent SK-type K channels, which is associated with an increase in neuronal excitability. In the hippocampus, SK-mediated intrinsic plasticity has been shown to play a role in trace eyeblink conditioning; however, it is not yet known how intrinsic plasticity contributes to a cerebellar learning task such as delay eyeblink conditioning. Whole cell recordings were obtained from acute cerebellar slices from mice ~48 hours after learning a delay eyeblink conditioning task. Over a period of repeated training sessions mice received either distinctly paired trials of a tone co-terminating with a periorbital shock (conditioned mice) or trials in which these stimuli were presented in an unpaired manner (pseudoconditioned mice). Conditioned mice show a significantly reduced afterhyperpolarization (AHP) following trains of parallel fiber stimuli. Moreover, we find that SK-dependent intrinsic plasticity is occluded in conditioned, but not pseudoconditioned mice. These findings show that excitability is enhanced in Purkinje cells after delay eyeblink conditioning and point toward a downregulation of SK channels as a potential underlying mechanism.

scholarly journals Profound Alterations in the Intrinsic Excitability of Cerebellar Purkinje Neurons Following Neurotoxin 3-Acetylpyridine (3-AP)-Induced Ataxia in Rat: New Insights Into the Role of Small Conductance K+ Channels

2011 ◽  
pp. 355-365 ◽  
Author(s):  
M. KAFFASHIAN ◽  
M. SHABANI ◽  
I. GOUDARZI ◽  
G. BEHZADI ◽  
A. ZALI ◽  
...  
Keyword(s):  
Neuronal Excitability ◽  
Input Resistance ◽  
Firing Frequency ◽  
Discharge Frequency ◽  
Sk Channels ◽  
Intrinsic Properties ◽  
K Channels ◽  
Initial Discharge ◽  
Small Conductance

Alterations in the intrinsic properties of Purkinje cells (PCs) may contribute to the abnormal motor performance observed in ataxic rats. To investigate whether such changes in the intrinsic neuronal excitability could be attributed to the role of Ca2+-activated K+ channels (KCa), whole cell current clamp recordings were made from PCs in cerebellar slices of control and ataxic rats. 3-AP induced profound alterations in the intrinsic properties of PCs, as evidenced by a significant increase in both the membrane input resistance and the initial discharge frequency, along with the disruption of the firing regularity. In control PCs, the blockade of small conductance KCa channels by UCL1684 resulted in a significant increase in the membrane input resistance, action potential (AP) half-width, time to peak of the AP and initial discharge frequency. SK channel blockade also significantly decreased the neuronal discharge regularity, the peak amplitude of the AP, the amplitude of the after- hyperpolarization and the spike frequency adaptation ratio. In contrast, in ataxic rats, both the firing regularity and the initial firing frequency were significantly increased by the blockade of SK channels. In conclusion, ataxia may arise from alterations in the functional contribution of SK channels, to the intrinsic properties of PCs.

scholarly journals Chronic Cortical Injury and Epileptogensis: A Possible Role for Intracellular Chloride Homeostasis

2005 ◽  
Vol 5 (6) ◽  
pp. 239-240 ◽  
Author(s):  
F. Edward Dudek ◽  
Kevin J. Staley
Keyword(s):  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Adult Rats ◽  
Positive Shift ◽  
Chloride Homeostasis ◽  
Mature Brain ◽  
Significant Difference ◽  
The Difference ◽  
Layer V ◽  
Patch Technique

Impaired Cl– Extrusion in Layer V Pyramidal Neurons of Chronically Injured Epileptogenic Neocortex Jin X, Huguenard JR, Prince DA J Neurophysiol 2005;93:2117–2126 In the mature brain, the K+/Cl– cotransporter KCC2 is important in maintaining low [Cl–]i, resulting in hyperpolarizing GABA responses. Decreases in KCC2 after neuronal injuries result in increases in [Cl–]i and enhanced neuronal excitability due to depolarizing GABA responses. We used the gramicidin perforated-patch technique to measure ECl(∼ EGABA) in layer V pyramidal neurons in slices of partially isolated sensorimotor cortex of adult rats to explore the potential functional consequence of KCC2 downregulation in chronically injured cortex. EGABA was measured by recording currents evoked with brief GABA puffs at various membrane potentials. No significant difference was found in ECl between neurons in control and undercut animals (–71.2 ± 2.6 and −71.8 ± 2.8 mV, respectively). However, when loaded with Cl– by applying muscimol puffs at 0.2 Hz for 60 seconds, neurons in the undercut cortex had a significantly shorter time constant for the positive shift in ECl during the Cl– loading phase (4.3 ± 0.5 s for control and 2.2 ± 0.4 s for undercut; p < 0.01). The positive shift in ECl 3 seconds after the beginning of Cl– loading was also significantly larger in the undercut group than in the control, indicating that neurons in undercut cortex were less effective in maintaining low [Cl–]i during repetitive activation of GABAA receptors. Application of furosemide eliminated the difference between the control and undercut groups for both of these measures of [Cl–]i regulation. The results suggest an impairment in Cl– extrusion resulting from decreased KCC2 expression that may reduce the strength of GABAergic inhibition and contribute to epileptogenesis.

scholarly journals Dendritic small conductance calcium-activated potassium channels activated by action potentials suppress EPSPs and gate spike-timing dependent synaptic plasticity

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Scott L Jones ◽  
Minh-Son To ◽  
Greg J Stuart
Keyword(s):  
Synaptic Plasticity ◽  
Potassium Channels ◽  
Action Potentials ◽  
Pyramidal Neurons ◽  
Receptor Activation ◽  
Spike Timing ◽  
Sk Channels ◽  
Sk Channel ◽  
Calcium Activated Potassium Channels ◽  
Small Conductance

Small conductance calcium-activated potassium channels (SK channels) are present in spines and can be activated by backpropagating action potentials (APs). This suggests they may play a critical role in spike-timing dependent synaptic plasticity (STDP). Consistent with this idea, EPSPs in both cortical and hippocampal pyramidal neurons were suppressed by preceding APs in an SK-dependent manner. In cortical pyramidal neurons EPSP suppression by preceding APs depended on their precise timing as well as the distance of activated synapses from the soma, was dendritic in origin, and involved SK-dependent suppression of NMDA receptor activation. As a result SK channel activation by backpropagating APs gated STDP induction during low-frequency AP-EPSP pairing, with both LTP and LTD absent under control conditions but present after SK channel block. These findings indicate that activation of SK channels in spines by backpropagating APs plays a key role in regulating both EPSP amplitude and STDP induction.

scholarly journals Location matters: somatic and dendritic SK channels answer to distinct calcium signals

2015 ◽  
Vol 114 (1) ◽  
pp. 1-5 ◽  
Author(s):  
Stephanie Rudolph ◽  
Monica S. Thanawala
Keyword(s):  
Calcium Imaging ◽  
Pyramidal Neurons ◽  
Sk Channels ◽  
Calcium Signals ◽  
Intracellular Signals ◽  
Voltage Dependent ◽  
Cortical Pyramidal Neurons ◽  
Voltage Dependent Calcium Channels ◽  
Signal Specificity ◽  
Small Conductance

Voltage-dependent calcium channels (VDCCs) couple neuronal activity to diverse intracellular signals with exquisite spatiotemporal specificity. Using calcium imaging and electrophysiology, Jones and Stuart ( J Neurosci 33: 19396–19405, 2013) examined the intimate relationship between distinct types of VDCCs and small-conductance calcium-activated potassium (SK) channels that contribute to the compartmentalized control of excitability in the soma and dendrites of cortical pyramidal neurons. Here we discuss the importance of calcium domains for signal specificity, explore the possible functions and mechanisms for local control of SK channels, and highlight technical considerations for the optical detection of calcium signals.

scholarly journals Increasing SK2 channel activity impairs associative learning

2012 ◽  
Vol 108 (3) ◽  
pp. 863-870 ◽  
Author(s):  
Bridget M. McKay ◽  
M. Matthew Oh ◽  
Roberto Galvez ◽  
Jeffrey Burgdorf ◽  
Roger A. Kroes ◽  
...  
Keyword(s):  
Associative Learning ◽  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Dorsal Hippocampus ◽  
Eyeblink Conditioning ◽  
Excitatory Postsynaptic Potential ◽  
Sk Channels ◽  
Hippocampal Pyramidal Neurons ◽  
Trace Eyeblink Conditioning

Enhanced intrinsic neuronal excitability of hippocampal pyramidal neurons via reductions in the postburst afterhyperpolarization (AHP) has been hypothesized to be a biomarker of successful learning. This is supported by considerable evidence that pharmacologic enhancement of neuronal excitability facilitates learning. However, it has yet to be demonstrated that pharmacologic reduction of neuronal excitability restricted to the hippocampus can retard acquisition of a hippocampus-dependent task. Thus, the present study was designed to address this latter point using a small conductance potassium (SK) channel activator NS309 focally applied to the dorsal hippocampus. SK channels are important contributors to intrinsic excitability, as measured by the medium postburst AHP. NS309 increased the medium AHP and reduced excitatory postsynaptic potential width of CA1 neurons in vitro. In vivo, NS309 reduced the spontaneous firing rate of CA1 pyramidal neurons and impaired trace eyeblink conditioning in rats. Conversely, trace eyeblink conditioning reduced levels of SK2 channel mRNA and protein in the hippocampus. Therefore, the present findings indicate that modulation of SK channels is an important cellular mechanism for associative learning and further support postburst AHP reductions in hippocampal pyramidal neurons as a biomarker of successful learning.

scholarly journals Cardiac small-conductance calcium-activated potassium channels in health and disease

2021 ◽  
Vol 473 (3) ◽  
pp. 477-489 ◽  
Author(s):  
Xiao-Dong Zhang ◽  
Phung N. Thai ◽  
Deborah K. Lieu ◽  
Nipavan Chiamvimonvat
Keyword(s):  
Ventricular Myocytes ◽  
Pulmonary Veins ◽  
Differential Sensitivity ◽  
Sk Channels ◽  
Sk Channel ◽  
Ventricular Cells ◽  
Intracellular Ca ◽  
Life Threatening ◽  
Health And Disease ◽  
Small Conductance

AbstractSmall-conductance Ca2+-activated K+ (SK, KCa2) channels are encoded by KCNN genes, including KCNN1, 2, and 3. The channels play critical roles in the regulation of cardiac excitability and are gated solely by beat-to-beat changes in intracellular Ca2+. The family of SK channels consists of three members with differential sensitivity to apamin. All three isoforms are expressed in human hearts. Studies over the past two decades have provided evidence to substantiate the pivotal roles of SK channels, not only in healthy heart but also with diseases including atrial fibrillation (AF), ventricular arrhythmia, and heart failure (HF). SK channels are prominently expressed in atrial myocytes and pacemaking cells, compared to ventricular cells. However, the channels are significantly upregulated in ventricular myocytes in HF and pulmonary veins in AF models. Interests in cardiac SK channels are further fueled by recent studies suggesting the possible roles of SK channels in human AF. Therefore, SK channel may represent a novel therapeutic target for atrial arrhythmias. Furthermore, SK channel function is significantly altered by human calmodulin (CaM) mutations, linked to life-threatening arrhythmia syndromes. The current review will summarize recent progress in our understanding of cardiac SK channels and the roles of SK channels in the heart in health and disease.

Sign in / Sign up

Export Citation Format

Share Document