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

Calcium-activated potassium (K(Ca)) channels are present throughout the central nervous system as well as many peripheral tissues. Activation of K(Ca) 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 K(Ca) 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 K(Ca)2 channels (K(Ca)2.1, K(Ca)2.2, and K(Ca)2.3) and the intermediate-conductance (K(Ca)3.1) channel. These channels are activated by submicromolar intracellular Ca(2+) concentrations and are voltage independent. Of all K(Ca) channels only the K(Ca)2 channels can be potently but differentially blocked by the bee-venom apamin. In the past few years modulation of K(Ca) channel activation revealed new roles for K(Ca)2 channels in controlling dendritic excitability, synaptic functioning, and synaptic plasticity. Furthermore, K(Ca)2 channels appeared to be involved in neurodegeneration, and learning and memory processes. In this review, we focus on the role of K(Ca)2 and K(Ca)3 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 K(Ca) channel activation.