IA Channels: Diverse Regulatory Mechanisms

In many peripheral and central neurons, A-type K+ currents, I-A, have been identified and shown to be key determinants in shaping action potential waveforms and repetitive firing properties, as well as in the regulation of synaptic transmission and synaptic plasticity. The functional properties and physiological roles of native neuronal I-A, however, have been shown to be quite diverse in different types of neurons. Accumulating evidence suggests that this functional diversity is generated by multiple mechanisms, including the expression and subcellular distributions of I-A channels encoded by different voltage-gated K+ (Kv) channel pore-forming (alpha) subunits, interactions of Kv alpha ubunits with cytosolic and/or transmembrane accessory subunits and regulatory proteins and post-translational modifications of channel subunits. Several recent reports further suggest that local protein translation in the dendrites of neurons and interactions between I-A channels with other types of voltage-gated ion channels further expands the functional diversity of native neuronal I-A channels. Here, we review the diverse molecular mechanisms that have been shown or proposed to underlie the functional diversity of native neuronal I-A channels.