SYMPOSIUM REVIEW: Going native: voltage-gated potassium channels controlling neuronal excitability

Abstract

In this review we take a physiological perspective on the role of voltage-gated potassium channels in an identified neuron in the auditory brainstem. The large number of KCN genes for potassium channel subunits and the heterogeneity of the subunit combination into K + channels make identification of native conductances especially difficult. We provide a general pharmacological and biophysical profile to help identify the common voltage-gated K + channel families in a neuron. Then we consider the physiological role of each of these conductances from the perspective of the principal neuron in the medial nucleus of the trapezoid body (MNTB). The MNTB is an inverting relay, converting excitation generated by sound from one cochlea into inhibition of brainstem nuclei on the opposite side of the brain; this information is crucial for binaural comparisons and sound localization. The important features of MNTB action potential (AP) firing are inferred from its inhibitory projections to four key target nuclei involved in sound localization (which is the foundation of auditory scene analysis in higher brain centres). These are: the medial superior olive (MSO), the lateral superior olive (LSO), the superior paraolivary nucleus (SPN) and the nuclei of the lateral lemniscus (NLL). The Kv families represented in the MNTB each have a distinct role: Kv1 raises AP firing threshold; Kv2 influences AP repolarization and hyperpolarizes the inter-AP membrane potential during high frequency firing; and Kv3 accelerates AP repolarization. These actions are considered in terms of fidelity of transmission, AP duration, firing rates and temporal jitter. An emerging theme is activity-dependent phosphorylation of Kv channel activity and suggests that intracellular signalling has a dynamic role in refining neuronal excitability and homeostasis.

Activity-dependent Phosphorylation of Neuronal Kv2.1 Potassium Channels by CDK5

“…Cells were harvested 48 h post-transfection and analyzed by immunoblot for Kv2.1 phosphorylated at Ser-603 (pS603) and total Kv2. ability and of the input-output relationships in mammalian neurons (34). A number of recent studies have provided valuable insights into the role of specific Kv channel subtypes in the processing and integration of synaptic input within the somatodendritic domain (35), initiation and propagation of axonal action potentials (36), and regulation of neurotransmitter release (37).…”

“…A number of recent studies have provided valuable insights into the role of specific Kv channel subtypes in the processing and integration of synaptic input within the somatodendritic domain (35), initiation and propagation of axonal action potentials (36), and regulation of neurotransmitter release (37). Modulation of the abundance, subcellular distribution, and gating of Kv channels through reversible multisite phosphorylation has emerged as a common theme for dynamic regulation of neuronal function (34,38,39) by allowing for integration between cell signaling pathways impacting the activity of specific neuronal PKs and PPs and the ion channels crucial for regulating neuronal excitability. Prominent examples include enhanced excitatory synaptic activity causing PKA-dependent phosphorylation and internalization of Kv4.2 in dendritic spines that results in enhancement of mEPSCs in hippocampal neurons (40,41) and high frequency auditory stimulation causing rapid dephosphorylation of Kv3.1, leading to the enhancement of Kv3.1 activity needed to support high frequency spiking in auditory neurons (42).…”

Phosphoinositide Modulation of Heteromeric Kv1 Channels Adjusts Output of Spiral Ganglion Neurons from Hearing Mice

“…In cultures of neonatal mouse SGNs, rapid adaptation is regulated by dendrotoxin-sensitive, low-threshold voltageactivated (LVA) K ϩ currents . The implication of a role for Kv1-family subunits has also been suggested in the auditory brain (Johnston et al, 2010). However, in SGNs cultured from adult guinea pigs, inhibition of LVA currents by dendrotoxin does not affect adaptation (Szabó et al, 2002), raising the possibility of developmental or interspecies differences in the contribution to the LVA current.…”

Modeling Binaural Responses in the Auditory Brainstem to Electric Stimulation of the Auditory Nerve

“…Low-threshold potassium (KLT) channels are widely expressed in auditory neurons specialized for rapid temporal processing, including neurons in the MSO, where neural sensitivity to ITD first arises (Eatock 2003;Svirskis et al 2004;Scott et al 2005;Johnston et al 2010;Mathews et al 2010). KLT currents enable neurons to accurately encode temporal information at high frequencies (Manis and Marx 1991;Trussell 1997Trussell , 1999Rothman and Manis 2003a).…”