Localization of a high threshold potassium channel in the rat cochlear nucleus

Abstract

Potassium channels play a major role in determining the pattern and frequency of neuronal firing. In the cochlear nucleus (CN), various morphologically defined types of neurons have different responses to a sound. We have previously identified one type of cloned K+ channel, termed Kv3.1, which is highly expressed in many auditory neurons. Expression studies indicate that Kv3.1 channels have an unusually high threshold for activation. In this study, we used both in situ hybridization and immunohistochemistry to examine the expression patterns of the Kv3.1 channel in the CN. In the ventral CN, bushy cells hybridized strongly with Kv3.1 specific probes and a subpopulation of stellate/multipolar cells hybridized with Kv3.1 probes. In the dorsal CN, pyramidal and large multipolar/giant cells expressed Kv3.1 mRNA. Abundant Kv3.1 immunolabeling was also observed in the CN. The pattern of immunolabeling revealed that the Kv3.1 protein is distributed along the soma, proximal dendrites, unmyelinated axons, and axon terminals of stained neurons. In the case of pyramidal and octopus cells, no immunolabeling was detected at the somata, even though these cells expressed Kv3.1 mRNA. Computer simulations were used to explore the functional role of the Kv3.1 channel. The simulations indicate that Kv3.1 conductances may contribute to repolarization of large synaptic potentials. When stimulated at high frequencies, the presence of Kv3.1 enhances the ability of a model cell with some of the features of bushy cells to follow high frequency input with temporal precision.

Modulation of the Kv3.1b Potassium Channel Isoform Adjusts the Fidelity of the Firing Pattern of Auditory Neurons

“…Computer modeling was performed using equations that have been used previously to model MNTB neurons (Wang et al, 1998) and other auditory neurons (Perney and Kaczmarek, 1997;Richardson and Kaczmarek, 2000). The model comprised a sodium current I Na , the Kv3.1 current I Kv3.1 , a low-threshold potassium current I LT , and a leakage conductance I L .…”

“…I LT and I Kv3.1 were simulated by the equations I LT ϭ g LT lr(Ϫ80 Ϫ V ) and I Kv3.1 ϭ g Kv3.1 n 3 (0.8 ϩ 0.2p)(Ϫ80 Ϫ V ). Evolution of the variables m, h, l, r, n, and p were determined by Hodgkin-Huxley-like equations as described previously (Perney and Kaczmarek, 1997). Parameters for the sodium current were as follows: g Na ϭ 0.5 S, k ␣m ϭ 76.4 msec Ϫ1 , ␣m ϭ 0.037 mV Ϫ1 , k ␤m ϭ 6.93 msec Ϫ1 , ␤m ϭ Ϫ0.043 mV Ϫ1 , and k ␣h ϭ 0.000533 msec Ϫ1 , ␣h ϭ Ϫ0.0909 mV Ϫ1 , k ␤h ϭ 7.87 msec Ϫ1 , and ␤h ϭ 0.0691 mV Ϫ1 .…”

“…Within the auditory brainstem, the Kv3.1 channel is expressed at high levels in spherical and globular bushy cells of the cochlear nucleus (Perney and Kaczmarek, 1997) and in principal neurons of the MNTB (Li et al, 2001), which receive a secure synaptic input from the globular bushy cells . The large calyx of Held synaptic ending from globular bushy cells onto the somata of MNTB neurons is specialized for temporally invariant transmission of excitatory inputs (Morest, 1968;Borst et al, 1995;Joris, 1996;Trussell, 1999), and evidence suggests that MNTB neurons faithfully transmit temporal information from globular bushy cells (Smith et al, 1998).…”

Ionic and neuromodulatory regulation of burst discharge controls frequency tuning

“…One mechanism used to encode specific aspects of the signal involves multiple neuronal representations ('maps') that differentially encode the same stimulus, as found in the auditory and olfactory systems. This often involves gradients of expression of specific ion channels as observed in the ELL (Deng et al, 2005;Ellis et al, 2007b;Mehaffey et al, 2006;Smith et al, 2006) and in mammalian auditory processing, in particular in the auditory brainstem (Li et al, 2001;Perney and Kaczmarek, 1997;von Hehn et al, 2004).…”

KCNE2 and the K+channel

“…94 In the CNS, Kv3 subunits facilitate rapid firing of neurons owing to their extremely rapid activation kinetics, particularly of Kv3.1 and Kv3.2. [95][96][97] These two delayed rectifier a subunits form heteromeric complexes with Kv3.4 and possibly Kv3.3, which in contrast are both N-type rapidly inactivating Kv a subunits. [98][99][100] For example, Kv3.1-Kv3.4 heteromers are expressed in fast-spiking neurons, where they facilitate rapid firing.…”