KCa2 and KCa3 Channels in Learning and Memory Processes, and Neurodegeneration

Abstract

Calcium-activated potassium (KCa) channels are present throughout the central nervous system as well as many peripheral tissues. Activation of KCa channels contribute to maintenance of the neuronal membrane potential and was shown to underlie the afterhyperpolarization (AHP) that regulates action potential firing and limits the firing frequency of repetitive action potentials. Different subtypes of KCa channels were anticipated on the basis of their physiological and pharmacological profiles, and cloning revealed two well defined but phylogenetic distantly related groups of channels. The group subject of this review includes both the small conductance KCa2 channels (KCa2.1, KCa2.2, and KCa2.3) and the intermediate-conductance (KCa3.1) channel. These channels are activated by submicromolar intracellular Ca2+ concentrations and are voltage independent. Of all KCa channels only the KCa2 channels can be potently but differentially blocked by the bee-venom apamin. In the past few years modulation of KCa channel activation revealed new roles for KCa2 channels in controlling dendritic excitability, synaptic functioning, and synaptic plasticity. Furthermore, KCa2 channels appeared to be involved in neurodegeneration, and learning and memory processes. In this review, we focus on the role of KCa2 and KCa3 channels in these latter mechanisms with emphasis on learning and memory, Alzheimer’s disease and on the interplay between neuroinflammation and different neurotransmitters/neuromodulators, their signaling components and KCa channel activation.

Stress-altered synaptic plasticity and DAMP signaling in the hippocampus-PFC axis; elucidating the significance of IGF-1/IGF-1R/CaMKIIα expression in neural changes associated with a prolonged exposure therapy

“…Physiologically, CaMKIIα regulates calcium-calmodulin - known to inhibit small ion conductance channels - in LTP (Grunnet et al, 2010; Mpari et al, 2010; Kuiper et al, 2012; Stackmam et al, 2008). Together, CaMKIIα, and these small channels occupy postsynaptic densities in the hippocampus (González et al, 2012; Trimmer, 2015).…”

Targeting of Tumor Necrosis Factor Alpha Receptors as a Therapeutic Strategy for Neurodegenerative Disorders

“…As such, it was suggested that in primary cortical neurons, TNF-α induces K(Ca)2.2 channel activation, resulting in neurons that are more resistant to excitotoxic cell death by preventing intracellular calcium levels to become pathologically high [129,205]. In the past years it has been shown that K(Ca)2 channels may also be involved in mechanisms contributing to the plasticity of the hippocampal CA1 neurons and in learning and memory [206,207]. Fischer et al (2014) showed that TNFR2-mediated activation of the PI3K-PKB/Akt pathway in primary astrocytes induces the expression of different neuroprotective genes, including the gene that encodes leukemia inhibitory factor (LIF) [208].…”

Antiarrhythmic Mechanisms of SK Channel Inhibition in the Rat Atrium

“…[1][2][3][4] The SK channel proteins SK1, SK2, and SK3 are encoded by KCNN1, KCNN2, and KCNN3 genes, respectively. 5 SK channels are characterized by their small single-channel conductance, activation by submicromolar [Ca 2+ ] i , voltage insensitivity, and selective blockade by the bee venom toxin apamin.…”