Impact of calcium-activated potassium channels on NMDA spikes in cortical layer 5 pyramidal neurons

Active electrical events play an important role in shaping signal processing in dendrites. As these events are usually associated with an increase in intracellular calcium, they are likely to be under the control of calcium-activated potassium channels. Here, we investigate the impact of calcium-activated potassium channels on N-methyl-d-aspartate (NMDA) receptor-dependent spikes, or NMDA spikes, evoked by glutamate iontophoresis onto basal dendrites of cortical layer 5 pyramidal neurons. We found that small-conductance calcium-activated potassium channels (SK channels) act to reduce NMDA spike amplitude but at the same time, also decrease the iontophoretic current required for their generation. This SK-mediated decrease in NMDA spike threshold was dependent on R-type voltage-gated calcium channels and indicates a counterintuitive, excitatory effect of SK channels on NMDA spike generation, whereas the capacity of SK channels to suppress NMDA spike amplitude is in line with the expected inhibitory action of potassium channels on dendritic excitability. Large-conductance calcium-activated potassium channels had no significant impact on NMDA spikes, indicating that these channels are either absent from basal dendrites or not activated by NMDA spikes. These experiments reveal complex and opposing interactions among NMDA receptors, SK channels, and voltage-gated calcium channels in basal dendrites of cortical layer 5 pyramidal neurons during NMDA spike generation, which are likely to play an important role in regulating the way these neurons integrate the thousands of synaptic inputs they receive.

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Dendritic spikes in apical oblique dendrites of cortical layer 5 pyramidal neurons

10.1101/2020.08.15.252080 ◽

2020 ◽

Cited By ~ 1

Author(s):

Michael Lawrence G. Castañares ◽

Greg J. Stuart ◽

Vincent R. Daria

Keyword(s):

Sensory Processing ◽

Pyramidal Neurons ◽

Low Frequency ◽

Cortical Layer ◽

Voltage Gated ◽

Voltage Gated Calcium Channels ◽

Basal Dendrites ◽

Dendritic Spikes ◽

Specific Computation

AbstractDendritic spikes in layer 5 pyramidal neurons (L5PNs) play a major role in cortical computation. While dendritic spikes have been studied extensively in apical and basal dendrites of L5PNs, whether oblique dendrites, which ramify in the input layers of the cortex, also generate dendritic spikes is unknown. Here we report the existence of dendritic spikes in apical oblique dendrites of L5PNs. In silico investigations indicate that oblique branch spikes are triggered by brief, low-frequency action potential (AP) trains (~40 Hz) and are characterized by a fast sodium spike followed by activation of voltage-gated calcium channels. In vitro experiments confirmed the existence of oblique branch spikes in L5PNs during brief AP trains at frequencies of around 60 Hz. Oblique branch spikes offer new insights into branch-specific computation in L5PNs and may be critical for sensory processing in the input layers of the cortex.

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Apamin-Sensitive Small Conductance Calcium-Activated Potassium Channels, through their Selective Coupling to Voltage-Gated Calcium Channels, Are Critical Determinants of the Precision, Pace, and Pattern of Action Potential Generation in Rat Subthalamic Nucleus NeuronsIn Vitro

Journal of Neuroscience ◽

10.1523/jneurosci.23-20-07525.2003 ◽

2003 ◽

Vol 23 (20) ◽

pp. 7525-7542 ◽

Cited By ~ 137

Author(s):

Nicholas E. Hallworth ◽

Charles J. Wilson ◽

Mark D. Bevan

Keyword(s):

Potassium Channels ◽

Calcium Channels ◽

Action Potential ◽

Subthalamic Nucleus ◽

Action Potential Generation ◽

Potential Generation ◽

Voltage Gated ◽

Voltage Gated Calcium Channels ◽

Calcium Activated Potassium Channels ◽

Small Conductance

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Presynaptic Paraneoplastic Disorders of the Neuromuscular Junction: An Update

Brain Sciences ◽

10.3390/brainsci11081035 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1035

Author(s):

Maria Pia Giannoccaro ◽

Patrizia Avoni ◽

Rocco Liguori

Keyword(s):

Potassium Channels ◽

Neuromuscular Junction ◽

Calcium Channels ◽

Myasthenia Gravis ◽

Neuromuscular Transmission ◽

Voltage Gated ◽

Voltage Gated Calcium Channels ◽

Immune Mediated ◽

Recent Developments ◽

Myasthenic Syndrome

The neuromuscular junction (NMJ) is the target of a variety of immune-mediated disorders, usually classified as presynaptic and postsynaptic, according to the site of the antigenic target and consequently of the neuromuscular transmission alteration. Although less common than the classical autoimmune postsynaptic myasthenia gravis, presynaptic disorders are important to recognize due to the frequent association with cancer. Lambert Eaton myasthenic syndrome is due to a presynaptic failure to release acetylcholine, caused by antibodies to the presynaptic voltage-gated calcium channels. Acquired neuromyotonia is a condition characterized by nerve hyperexcitability often due to the presence of antibodies against proteins associated with voltage-gated potassium channels. This review will focus on the recent developments in the autoimmune presynaptic disorders of the NMJ.

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