Contribution of the Kv3.1 potassium channel to high‐frequency firing in mouse auditory neurones

Abstract

Using a combination of patch‐clamp, in situ hybridization and computer simulation techniques, we have analysed the contribution of potassium channels to the ability of a subset of mouse auditory neurones to fire at high frequencies. Voltage‐clamp recordings from the principal neurones of the medial nucleus of the trapezoid body (MNTB) revealed a low‐threshold dendrotoxin (DTX)‐sensitive current (ILT) and a high‐threshold DTX‐insensitive current (IHT). I HT displayed rapid activation and deactivation kinetics, and was selectively blocked by a low concentration of tetraethylammonium (TEA; 1 mm). The physiological and pharmacological properties of IHT very closely matched those of the Shaw family potassium channel Kv3.1 stably expressed in a CHO cell line. An mRNA probe corresponding to the C‐terminus of the Kv3.1 channel strongly labelled MNTB neurones, suggesting that this channel is expressed in these neurones. TEA did not alter the ability of MNTB neurones to follow stimulation up to 200 Hz, but specifically reduced their ability to follow higher frequency impulses. A computer simulation, using a model cell in which an outward current with the kinetics and voltage dependence of the Kv3.1 channel was incorporated, also confirmed that the Kv3.1‐ like current is essential for cells to respond to a sustained train of high‐frequency stimuli. We conclude that in mouse MNTB neurones the Kv3.1 channel contributes to the ability of these cells to lock their firing to high‐frequency inputs.

Coding interaural time differences at low best frequencies in the barn owl

“…Voltage sensitive K þ conductances determine the response properties of auditory neurons, and each cell type exhibits a distinct complement of outward K þ currents [3,67,77,123]. At least two K þ conductances underlie phase locked responses in auditory neurons: a low and a high threshold conductance [11,67,90,91,120].…”

“…This has the effect of minimizing Na þ channel inactivation, allowing cells to reach firing threshold sooner and facilitating high frequency firing. Elimination of the Kv3.1 gene in mice results in the loss of a high-threshold component of potassium current and failure of the neurons to follow high-frequency stimulation [65,120]. Brief action potentials also reduce the amount of neurotransmitter released [99].…”

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

“…Such cells lock their action potentials precisely to the phase of auditory stimuli at frequencies of up to 2000 -4000 Hz or to rapid fluctuations in the amplitude of higher-frequencies sounds (Joris and Yin, 1995;Joris, 1996). At those frequencies at which an action potential cannot be generated to every single stimulus, their firing pattern is characterized by alternating action potentials and failures of action potential generation (Banks and Smith, 1992;Brew and Forsythe, 1995;Wang et al, 1998). For example, in response to a 600 Hz stimulus, an MNTB neuron may fire at 300 Hz, locking its action potentials to every other stimulus (Wang et al, 1998).…”

Inhibition of Ca2+-activated large-conductance K+ channel activity alters synaptic AMPA receptor phenotype in mouse cerebellar stellate cells

“…We therefore tested whether these channels contribute to the net K ϩ current in stellate cells. A low concentration of TEA is known to block preferentially a subset of K ϩ channels, including Kv3 and BK channels (Rudy and McBain 2001;Wang et al 1998). We found that bath application of 1 mM TEA reduced the outward transient current at 0 mV by 53.2 Ϯ 1.8% and the noninactivating current by 42.8 Ϯ 6.2% (n ϭ 4; P Ͻ 0.05; Fig.…”

“…These channels display a characteristic high activation threshold and generate noninactivating currents, which accelerate the repolarization of APs. These properties reduce the AP duration and allow neurons to fire APs at high frequency (Salkoff et al 2006;Wang et al 1998). One intriguing possibility is that the brief duration of such APs suppresses the expression of GluR2 subunits in these neurons.…”