Neurons from varied regions of the central nervous system can show widely divergent responses to electrical stimuli that are determined by cell-specific differences in ion channel composition. The well-ordered and highly characterized peripheral auditory system allows one to explore the significance of this diversity during the final stages of postnatal development. We examined the electrophysiological features of murine spiral ganglion neurons in vitro at a time when recordings could be made from the cell bodies before myelination. These cells carry information about sound stimuli from hair cell receptors in the basilar membrane and are arranged tonotopically. Spiral ganglion neuron responses to depolarizing current injection were assessed with whole-cell current clamp recordings from cells that were isolated separately from the apical and basal thirds of the mouse cochlea. These cells displayed systematic variation in their firing. Apex neurons (low frequency coding) showed longer latency, slowly adapting responses, whereas base neurons (high frequency coding) showed short latency, rapidly adapting responses to the same stimuli. This physiological diversity was mirrored by regional differences in ion channel content assessed immunohistochemically. Apex neurons had a preponderance of Kv4.2 subunits, whereas base neurons possessed greater levels of K(Ca), Kv1.1, and Kv3.1 subunits. Taken together, these results indicate that the distribution of a set of voltage-gated potassium channels may relate specifically to a particular range of coding frequencies. These studies also suggest that intrinsic properties of spiral ganglion neurons can contribute to the characteristic responses of the peripheral auditory system. Their potential role in development and adult function is discussed.
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.
Current-clamp recordings with the use of the whole cell configuration of the patch-clamp technique were made from postnatal mouse spiral ganglion neurons in vitro. Cultures contained neurons that displayed monopolar, bipolar, and pseudomonopolar morphologies. Additionally, a class of neurons having exceptionally large somata was observed. Frequency histograms of the maximum number of action potentials fired from 240-ms step depolarizations showed that neurons could be classified as either slowly adapting or rapidly adapting. Most neurons (85%) were in the rapidly adapting category (58 of 68 recordings). Measurements of elementary properties were used to define the endogenous firing characteristics of both the neuron classes. Action potential number varied with step and holding potential, spike amplitude decayed during prolonged depolarizations, and spike frequency adaptation was observed in both rapidly and slowly adapting neurons. The apparent input resistance, spike amplitude decrement, and instantaneous firing frequency differed significantly between rapidly and slow adapting neurons. Inward rectification was evaluated in response to hyperpolarizing contrast current injections. Present in both electrophysiological classes, its magnitude was graded from neuron to neuron, reflecting differences in number, type, and/or voltage dependence of the underlying channels. These data suggest that spiral ganglion neurons possess intrinsic firing properties that regulate action potential number and timing, features that may be crucial to signal coding in the auditory periphery.
Inward rectification was characterized in neonatal spiral ganglion neurons maintained in tissue culture. Whole cell current and voltage-clamp techniques were used to show that the hyperpolarization-activated cationic (Ih) current underlies most or all of the inward rectification demonstrated in these neurons. The average reversal potential (-41.3 mV) and cesium sensitivity were typical of that found in other neurons and cell types. What was unique about the hyperpolarization-activated currents, however, was that the half-maximal voltages (V1/2) and slope factors (k) that characterized Ih current activation were graded from neuron to neuron. Voltage-clamp recordings made with standard bath and pipette solutions revealed V1/2 values that ranged from -78.1 to -122.1 mV, with slope factors from 7.6 to 13.1. These gradations in the voltage-dependent features of the Ih current did not result from variability in the recording conditions because independently measured Na+ current-to-voltage relationships were found to be uniform (peak current at -20 mV). Moreover, the range and average V1/2 and slope values could be altered with activators [8-(4-chlorophenylthio) adenosine 3',5'-cyclic monophosphate in combination with okadaic acid] or inhibitors {N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide}of protein indicating that Ih current heterogeneity most likely resulted from differential phosphorylation.
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