Nonselective Cation Channels and Links to Hippocampal Ischemia, Aging, and Dementia

MacDonald, John F.; Belrose, Jillian C.; Xie, Yu-Feng; Jackson, Michael

doi:10.1007/978-1-4614-4756-6_37

Cited by 6 publications

(4 citation statements)

References 144 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the brain, the K V 4 channel expression depends on the neuron type and region, and continuous efforts are made to unravel the organization of these channels in different subcellular compartments and neuron types [11,12]. In hippocampus, K V 4 channelopathies are linked to schizophrenia, epilepsy, and Alzheimer's disease [13][14][15]. Hence, the pharmacological modulation of I TO and I SA may have therapeutic value in the treatment of these pathologies.…”

Section: Introductionmentioning

confidence: 99%

Pharmacological Approaches for the Modulation of the Potassium Channel KV4.x and KChIPs

Cercós

Peraza

Benito-Bueno

et al. 2021

IJMS

View full text Add to dashboard Cite

Ion channels are macromolecular complexes present in the plasma membrane and intracellular organelles of cells. Dysfunction of ion channels results in a group of disorders named channelopathies, which represent an extraordinary challenge for study and treatment. In this review, we will focus on voltage-gated potassium channels (KV), specifically on the KV4-family. The activation of these channels generates outward currents operating at subthreshold membrane potentials as recorded from myocardial cells (ITO, transient outward current) and from the somata of hippocampal neurons (ISA). In the heart, KV4 dysfunctions are related to Brugada syndrome, atrial fibrillation, hypertrophy, and heart failure. In hippocampus, KV4.x channelopathies are linked to schizophrenia, epilepsy, and Alzheimer’s disease. KV4.x channels need to assemble with other accessory subunits (β) to fully reproduce the ITO and ISA currents. β Subunits affect channel gating and/or the traffic to the plasma membrane, and their dysfunctions may influence channel pharmacology. Among KV4 regulatory subunits, this review aims to analyze the KV4/KChIPs interaction and the effect of small molecule KChIP ligands in the A-type currents generated by the modulation of the KV4/KChIP channel complex. Knowledge gained from structural and functional studies using activators or inhibitors of the potassium current mediated by KV4/KChIPs will better help understand the underlying mechanism involving KV4-mediated-channelopathies, establishing the foundations for drug discovery, and hence their treatments.

show abstract

Section: Introductionmentioning

confidence: 99%

Pharmacological Approaches for the Modulation of the Potassium Channel KV4.x and KChIPs

Cercós

Peraza

Benito-Bueno

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…Intrinsic activity depends on electrical signals largely determined by ion channels operating along the neuronal plasma membrane. The dysfunction of ion channels known to regulate hippocampal neurophysiology is linked to pathologies including schizophrenia, epilepsy and Alzheimer’s disease [2,3].…”

Section: Introductionmentioning

confidence: 99%

Expression, Cellular and Subcellular Localisation of Kv4.2 and Kv4.3 Channels in the Rodent Hippocampus

Alfaro-Ruiz

Aguado

Martín-Belmonte

et al. 2019

IJMS

View full text Add to dashboard Cite

The Kv4 family of voltage-gated K+ channels underlie the fast transient (A-type) outward K+ current. Although A-type currents are critical to determine somato-dendritic integration in central neurons, relatively little is known about the precise subcellular localisation of the underlying channels in hippocampal circuits. Using histoblot and immunoelectron microscopic techniques, we investigated the expression, regional distribution and subcellular localisation of Kv4.2 and Kv4.3 in the adult brain, as well as the ontogeny of their expression during postnatal development. Histoblot demonstrated that Kv4.2 and Kv4.3 proteins were widely expressed in the brain, with mostly non-overlapping patterns. During development, levels of Kv4.2 and Kv4.3 increased with age but showed marked region- and developmental stage-specific differences. Immunoelectron microscopy showed that labelling for Kv4.2 and Kv4.3 was differentially present in somato-dendritic domains of hippocampal principal cells and interneurons, including the synaptic specialisation. Quantitative analyses indicated that most immunoparticles for Kv4.2 and Kv4.3 were associated with the plasma membrane in dendritic spines and shafts, and that the two channels showed very similar distribution patterns in spines of principal cells and along the surface of granule cells. Our data shed new light on the subcellular localisation of Kv4 channels and provide evidence for their non-uniform distribution over the plasma membrane of hippocampal neurons.

show abstract

“…These and other functions of principal cells depend on electrical signals, the generation, patterns, and propagation of which are determined largely by the complement of ion channels that they express. Indeed, the dysfunction of ion channels known to regulate hippocampal neurophysiology is linked to pathologies including schizophrenia, epilepsy and Alzheimer's disease (Poolos & Johnston, 2012;MacDonald et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Differential subcellular localization of SK3‐containing channels in the hippocampus

Ballesteros-Merino

Watanabe

Shigemoto

et al. 2014

Eur J of Neuroscience

View full text Add to dashboard Cite

Small-conductance, Ca(2+) -activated K(+) (SK) channels are expressed in the hippocampus where they regulate synaptic responses, plasticity, and learning and memory. To investigate the expression of SK3 (KCNN3) subunits, we determined the developmental profile and subcellular distribution of SK3 in the developing mouse hippocampus using western blots, immunohistochemistry and high-resolution immunoelectron microscopy. The results showed that SK3 expression increased during postnatal development, and that the localization of SK3 changed from being mainly associated with the endoplasmic reticulum and intracellular sites during the first postnatal week to being progressively concentrated in dendritic spines during later stages. In the adult, SK3 was localized mainly in postsynaptic compartments, both at extrasynaptic sites and along the postsynaptic density of excitatory synapses. Double labelling showed that SK3 co-localized with SK2 (KCNN2) and with N-methyl-D-aspartate receptors. Finally, quantitative analysis of SK3 density revealed two subcellular distribution patterns in different hippocampal layers, with SK3 being unevenly distributed in CA1 region of the hippocampus pyramidal cells and homogeneously distributed in dentate gyrus granule cells. Our results revealed a complex cell surface distribution of SK3-containing channels and a distinct developmental program that may influence different hippocampal functions.

show abstract

Nonselective Cation Channels and Links to Hippocampal Ischemia, Aging, and Dementia

Cited by 6 publications

References 144 publications

Pharmacological Approaches for the Modulation of the Potassium Channel KV4.x and KChIPs

Pharmacological Approaches for the Modulation of the Potassium Channel KV4.x and KChIPs

Expression, Cellular and Subcellular Localisation of Kv4.2 and Kv4.3 Channels in the Rodent Hippocampus

Differential subcellular localization of SK3‐containing channels in the hippocampus

Contact Info

Product

Resources

About