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.
Highlights
It is widely accepted that the trigger for neurotransmitter release is the entry of calcium ions (Ca2+) into the presynaptic terminal (Ghosh and Greenberg, 1995)
Slow hyperpolarizing effects observed after stimulation of adrenergic, cholinergic, or purinergic pathways in smooth muscles of the gastrointestinal tract were caused by such an increase in K+ permeability as detected by the use of apamin (Banks et al, 1979; Maas and Den Hertog, 1979; Shuba and Vladimirova, 1980; Den Hertog, 1982)
Because interstitial cells of Cajal (ICC) have been identified as pacemaker cells and are known to play a major role in generating the regular motility of the gastrointestinal tract, these findings suggest that KCa2.3 channels, which are expressed in ICC, play an important role in generating a rhythmic pacemaker current in the gastrointestinal tract (Fujita et al, 2001)
Summary
It is widely accepted that the trigger for neurotransmitter release is the entry of calcium ions (Ca2+) into the presynaptic terminal (Ghosh and Greenberg, 1995). Slow hyperpolarizing effects observed after stimulation of adrenergic, cholinergic, or purinergic pathways in smooth muscles of the gastrointestinal tract were caused by such an increase in K+ permeability as detected by the use of apamin (Banks et al, 1979; Maas and Den Hertog, 1979; Shuba and Vladimirova, 1980; Den Hertog, 1982). This neurotoxic polypeptide was isolated from bee-venom and, when injected in rodents in purified form, exerted severe uncoordinated movements of the skeletal musculature increasing to spasms and convulsions of apparently spinal origin after a dose-dependent lag time (Habermann, 1984). Voltage-insensitive Ca2+-activated K+ channels of the small conductance-type (KCa) were later identified to carry these apamin-sensitive currents (Blatz and Magleby, 1986)
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