Functional and Molecular Diversity of Native Neuronal K ⁺ Channels

Abstract

Multiple types of potassium (K + ) currents have been distinguished in central and peripheral neurons based on differences in gating, time-and voltage-dependent properties and pharmacological sensitivities. The various K + currents function to control neuronal resting membrane potentials, action potential waveforms and repetitive firing properties. In addition, the cellular and sub-cellular expression patterns of the underlying K + channels are distinct, suggesting unique roles in regulating axonal and dendritic excitability and mediating the responses to synaptic inputs, as well as influencing short-and long-term changes in neuronal functioning, plasticity and homeostasis. Molecular cloning has revealed considerable diversity of K + channel pore-forming ( ) and of cytosolic and transmembrane accessory ( ) subunits, and accumulating evidence suggests that native neuronal K + channels, like other types of ion channels, function in macromolecular protein complexes. The individual (or combinations of) channel accessory subunits in these complexes, post-translational modifications of channel subunits, as well as interactions with intracellular mediators and other types of voltage-gated ion channels, influence the properties and the functioning of neuronal K + channels. The theme of this article is the electrophysiological and molecular diversity of neuronal K + channels and the molecular mechanisms that control the expression, distribution and functioning of native neuronal K + channels with a focus on rapidly activating and inactivating voltage-gated A-type K + channels for illustrative purposes.