Na(+)-activated K(+) (K(Na)) channels are expressed in neurons and are activated by Na(+) influx through voltage-dependent channels or ionotropic receptors, yet their function remains unclear. Here we show that K(Na) channels are associated with AMPA receptors and that their activation depresses synaptic responses. Synaptic activation of K(Na) channels by Na(+) transients via AMPA receptors shapes the decay of AMPA-mediated current as well as the amplitude of the synaptic potential. Thus, the coupling between K(Na) channels and AMPA receptors by synaptically induced Na(+) transients represents an inherent negative feedback mechanism that scales down the magnitude of excitatory synaptic responses.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2634910 | PMC |
| http://dx.doi.org/10.1073/pnas.0806403106 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Dystonia caused by ANO3 variants is due to attenuated Ca influx by ORAI1.
BMC Med
January 2025
Physiological Institute, University of Regensburg, University Street 31, 93053, Regensburg, Germany.
Background: Dystonia is a common neurological hyperkinetic movement disorder that can be caused by mutations in anoctamin 3 (ANO3, TMEM16C), a phospholipid scramblase and ion channel. We previously reported patients that were heterozygous for the ANO3 variants S651N, V561L, A599D and S651N, which cause dystonia by unknown mechanisms.
Methods: We applied electrophysiology, Ca measurements and cell biological methods to analyze the molecular mechanisms that lead to aberrant intracellular Ca signals and defective activation of K channels in patients heterozygous for the ANO3 variants.
Heterozygous expression of a gain-of-function variant has differential effects on somatostatin- and parvalbumin-expressing cortical GABAergic neurons.
Elife
October 2024
Fralin Biomedical Research Institute at Virginia Tech Carilion, Center for Neurobiology Research, Roanoke, United States.
Article Synopsis
- * In mouse studies, a specific GOF variant was examined, revealing that while it did not affect glutamatergic or VIP neurons, it caused SST neurons to become less excitable and PV neurons to become more excitable, both affecting their electrical activity.
- * The functional differences in SST and PV neurons were attributed to an increased persistent sodium current in PV neurons, showing that the pathogenic mechanisms can lead to opposite effects in similar neuron types and highlighting the complexity of treatment approaches for these disorders.
Disease-causing Slack potassium channel mutations produce opposite effects on excitability of excitatory and inhibitory neurons.
Cell Rep
March 2024
Department of Pharmacology, Yale School of Medicine, New Haven, CT 06520, USA; Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT 06520, USA. Electronic address:
The KCNT1 gene encodes the sodium-activated potassium channel Slack (KCNT1, K1.1), a regulator of neuronal excitability. Gain-of-function mutations in humans cause cortical network hyperexcitability, seizures, and severe intellectual disability.
View Article and Find Full Text PDFInteraction Between HCN and Slack Channels Regulates mPFC Pyramidal Cell Excitability in Working Memory Circuits.
Mol Neurobiol
April 2024
Department of Pharmacology, Yale School of Medicine, New Haven, CT, 06520, USA.
The ability of monkeys and rats to carry out spatial working memory tasks has been shown to depend on the persistent firing of pyramidal cells in the prefrontal cortex (PFC), arising from recurrent excitatory connections on dendritic spines. These spines express hyperpolarization-activated cyclic nucleotide-gated (HCN) channels whose open state is increased by cAMP signaling, and which markedly alter PFC network connectivity and neuronal firing. In traditional neural circuits, activation of these non-selective cation channels leads to neuronal depolarization and increased firing rate.
View Article and Find Full Text PDFHeterozygous expression of a gain-of-function variant has differential effects on SST- and PV-expressing cortical GABAergic neurons.
bioRxiv
August 2024
Fralin Biomedical Research Institute at Virginia Tech Carilion, Center for Neurobiology Research, Roanoke, VA, USA.
More than twenty recurrent missense gain-of-function (GOF) mutations have been identified in the sodium-activated potassium (K) channel gene in patients with severe developmental and epileptic encephalopathies (DEEs), most of which are resistant to current therapies. Defining the neuron types most vulnerable to KCNT1 GOF will advance our understanding of disease mechanisms and provide refined targets for precision therapy efforts. Here, we assessed the effects of heterozygous expression of a GOF variant (Y777H) on K currents and neuronal physiology among cortical glutamatergic and GABAergic neurons in mice, including those expressing vasoactive intestinal polypeptide (VIP), somatostatin (SST), and parvalbumin (PV), to identify and model the pathogenic mechanisms of autosomal dominant GOF variants in DEEs.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!