Dendrotoxin‐sensitive K⁺ currents contribute to accommodation in murine spiral ganglion neurons

Abstract

We have previously identified two broad electrophysiological classes of spiral ganglion neuron that differ in their rate of accommodation (Mo & Davis, 1997a). In order to understand the underlying ionic basis of these characteristic firing patterns, we used α‐dendrotoxin (α‐DTX) to eliminate the contribution of a class of voltage‐gated K+ channels and assessed its effects on a variety of electrophysiological properties by using the whole‐cell configuration of the patch‐clamp technique. Exposure to α‐DTX caused neurons that initially displayed rapid accommodation to fire continuously during 240 ms depolarizing test pulses within a restricted voltage range. We found a non‐monotonic relationship between number of action potentials fired and membrane potential in the presence of α‐DTX that peaked at voltages between –40 to –10 mV and declined at more depolarized and hyperpolarized test potentials. The α‐DTX‐sensitive current had two components that activated in different voltage ranges. Analysis of recordings made from acutely isolated neurons gave estimated half‐maximal activation voltages of –63 and 12 mV for the two components. Because α‐DTX blocks the Kv1.1, Kv1.2 and Kv1.6 subunits, we examined the action of the Kv1.1‐selective blocker dendrotoxin K (DTX‐K). We found that this antagonist reproduced the effects of α‐DTX on neuronal firing, and that the DTX‐K‐sensitive current also had two separate components. These data suggest that the transformation from a rapidly adapting to a slowly adapting firing pattern was mediated by the low voltage‐activated component of DTX‐sensitive current with a potential contribution from the high voltage‐activated component at more depolarized potentials. In addition, the effects of DTX‐K indicate that Kv1.1 subunits are important constituents of the underlying voltage‐gated potassium channels.

Complex Regulation of Spiral Ganglion Neuron Firing Patterns by Neurotrophin-3

“…We wished to determine, therefore, whether NT-3 would affect the magnitude or time course of voltage changes in response to step hyperpolarizing constant-current injections that reflect the activity of the I h currents. To avoid the contribution of other low-voltage-activated currents found in spiral ganglion neurons, such as Kv1.1 (Mo et al, 2002), measurements were made from relatively hyperpolarized levels (Ϫ185 Ϯ 3 mV) to the plateau level at the end of a 240 ms duration current injection. Our analysis showed no significant differences between any of the conditions (Fig.…”

Firing Patterns of Type II Spiral Ganglion NeuronsIn Vitro

“…Despite the fact that electrophysiological threshold was significantly different only between the basal type I and II neurons, the magnitude of the inward rectification differed significantly from the type I neurons for both apical and basal type II spiral ganglion neurons. Because the inward rectification is caused by I h currents, which have been identified in the spiral ganglion neurons (Mo et al, 2002), and the relationship between the I h currents and threshold has been convincingly established by others (Pape and McCormick, 1989;McCormick and Huguenard, 1992;Erickson et al, 1993), we speculate that it may also play a role in regulating the electrophysiological thresholds in spiral ganglion neurons.…”

“…Conversely, the stellate cells of the cochlear nucleus receive profuse synaptic connections and display slow accommodation (Oertel et al, 1988). Both centrally and peripherally, the low-threshold K ϩ currents that contribute to neuronal accommodation (Manis and Marx, 1991;Brew and Forsythe 1995;Rathouz and Trussell, 1998;Mo et al, 2002;Brew et al, 2003) appear to represent an intrinsic specialization that contributes to the exquisite temporal resolution observed in certain auditory nuclei (Oertel, 1997;Trussell, 1999).…”

“…For these experiments spiral ganglion neurons were colabeled with peripherin-␤-tubulin and Kv1.1 antibodies (see Materials and Methods). We chose to examine the Kv1.1 ion channel subunit because previous experiments from our laboratory had shown that rapidly accommodating neurons exposed to specific Kv1.1/ Kv1.2/Kv1.6 blockers [␣-dendrotoxin (DTX) and DTX-K] became slowly accommodating (Mo et al, 2002). The Kv1.1 subunit, therefore, contributes to limiting the number of action potentials that spiral ganglion neurons can fire in response to prolonged stimuli, and their relative density should relate to the electrophysiological measurements of AP max .…”

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

“…In dissociated spiral ganglion cultures, where there is a lack of IHC synaptic input, SGNs display heterogeneous adaptive responses to maintained current injection (Mo and Davis, 1997;Lv et al, 2012). Although the relative distribution of adaptation rates differs between studies, a consistent observation is the predominance of very rapidly adapting (phasic firing) cells.…”