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 (α) and of cytosolic and transmembrane accessory (β) 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. Key Concepts Multiple types of voltage‐dependent and voltage‐independent K + currents have been distinguished in mammalian peripheral and central neurons based on differences in biophysical and pharmacological properties. The electrophysiological diversity of neuronal K + currents has a functional significance in that the different K + currents contribute to determining resting membrane potentials, action potential waveforms, repetitive firing properties and responses to neurotransmitters and modulators. In most mammalian neurons, multiple functionally distinct types of K + currents/channels are co‐expressed and several are differentially distributed in neuronal cell bodies, dendrites and axons. A rather large number of K + ‐channel pore‐forming (α) subunits have been identified, many of which are expressed in peripheral and in central neurons, and considerable progress has been made in defining the relationships between the expressed K + ‐channel α subunits and functional neuronal K + channels. A number of cytosolic and transmembrane K + ‐channel auxiliary subunits have also been identified, and increasing evidence suggests that neuronal K + channels function in macromolecular protein complexes. Multiple transcriptional, post‐transcriptional, and post‐translational mechanisms contribute to native neuronal K + ‐channel diversity, distribution and functioning.