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Pyramidal neurons of the electrosensory lateral line lobe (ELL) of Apteronotus leptorhynchus express Kv3-type voltage-gated potassium channels that give rise to high-threshold currents at the somatic and dendritic levels. Two members of the Kv3 channel family, AptKv3.1 and AptKv3.3, are coexpressed in these neurons. AptKv3.3 channels are expressed at uniformly high levels in each of four ELL segments, whereas AptKv3.1 channels appear to be expressed in a graded manner with higher levels of expression in segments that process high-frequency electrosensory signals. Immunohistochemical and recombinant channel expression studies show a differential distribution of these two channels in the dendrites of ELL pyramidal neurons. AptKv3.1 is concentrated in somas and proximal dendrites, whereas AptKv3.3 is distributed throughout the full extent of the large dendritic tree. Recombinant channel expression of AptKv3 channels through in vivo viral injections allowed directed retargeting of AptKv3 subtypes over the somadendritic axis, revealing that the sequence responsible for targeting channels to distal dendrites lies within the C-terminal domain of the AptKv3.3 protein. The targeting domain includes a consensus sequence predicted to bind to a PDZ (postsynaptic density-95/Discs large/zona occludens-1)-type protein-protein interaction motif. These findings reveal that different functional roles for Kv3 potassium channels at the somatic and dendritic level of a sensory neuron are attained through specific targeting that selectively distributes Kv3.3 channels to the dendritic compartment.

Gamma frequencies of burst discharge (>40 Hz) have become recognized in select cortical and non-cortical regions as being important in feature extraction, neural synchrony and oscillatory discharge. Pyramidal cells of the electrosensory lateral line lobe (ELL) of Apteronotus leptorhynchus generate burst discharge in relation to specific features of sensory input in vivo that resemble those recognized as gamma frequency discharge when examined in vitro. We have shown that these bursts are generated by an entirely novel mechanism termed conditional backpropagation that involves an intermittent failure of dendritic Na+ spike conduction. Conditional backpropagation arises from a frequency-dependent broadening of dendritic spikes during repetitive discharge, and a mismatch between the refractory periods of somatic and dendritic spikes. A high threshold class of K+ channel, AptKv3.3, is expressed at high levels and distributed over the entire soma-dendritic axis of pyramidal cells. AptKv3.3 channels are shown to contribute to the repolarization of both somatic and dendritic spikes, with pharmacological blockade of dendritic Kv3 channels revealing an important role in controlling the threshold for burst discharge. The entire process of conditional back-propagation and burst output is successfully simulated using a new compartmental model of pyramidal cells that incorporates a cumulative inactivation of dendritic K+ channels during repetitive discharge. This work is important in demonstrating how the success of spike backpropagation can control the output of a principle sensory neuron, and how this process is regulated by the distribution and properties of voltage-dependent K+ channels.

The expression pattern and subcellular distribution of a teleost homologue of the mammalian Kv3.3 potassium channel, AptKv3.3, was examined in the electrosensory lateral line lobe (ELL) and two cerebellar lobes in the hindbrain of the weakly electric gymnotiform Apteronotus leptorhynchus. AptKv3.3 expression was brain specific, with the highest level of expression in the cerebellum and 56% relative expression in the ELL. In situ hybridization revealed that AptKv3.3 mRNA was present in virtually all cell classes in the ELL as well as in the cerebellar lobes eminentia granularis pars posterior (EGp) and corpus cerebellum (CCb). Immunocytochemistry indicated a distribution of AptKv3.3 channels over the entire soma-dendritic axis of ELL pyramidal, granule, and polymorphic cells and over the soma and at least proximal dendrites (100 microm) of multipolar cells and neurons of the ventral molecular layer. AptKv3.3 immunolabel was present at the soma of cerebellar granule, golgi, eurydendroid, and CCb Purkinje cells, with an equally intense label throughout the dendrites of CCb Purkinje cells and EGp eurydendroid cells. Immunolabel was virtually absent in afferent or efferent axon tracts of the ELL but was detected on climbing fiber axons and on the axons and putative terminal boutons of CCb Purkinje cells. These data reveal a prominent soma-dendritic distribution of AptKv3.3 K+ channels in both principal output and local circuit neurons, a pattern that is distinct from the soma-axonal distribution that characterizes all other Kv3 K+ channels examined to date. The widespread distribution of AptKv3.3 immunolabel in electrosensory cells implies an important role in several aspects of signal processing., (Copyright 2001 Wiley-Liss, Inc.)

Voltage-gated ion channels localized to dendritic membranes can shape signal processing in central neurons. This study describes the distribution and functional role of a high voltage-activating K(+) channel in the electrosensory lobe (ELL) of an apteronotid weakly electric fish. We identify a homolog of the Kv3.3 K(+) channel, AptKv3.3, that exhibits a high density of mRNA expression and immunolabel that is distributed over the entire soma-dendritic axis of ELL pyramidal cells. The kinetics and pharmacology of native K(+) channels recorded in pyramidal cell somata and apical dendrites match those of AptKv3.3 channels expressed in a heterologous expression system. The functional role of AptKv3.3 channels was assessed using focal drug ejections in somatic and dendritic regions of an in vitro slice preparation. Local blockade of AptKv3.3 channels slows the repolarization of spikes in pyramidal cell somata as well as spikes backpropagating into apical dendrites. The resulting increase in dendritic spike duration lowers the threshold for a gamma-frequency burst discharge that is driven by inward current associated with backpropagating dendritic spikes. Thus, dendritic AptKv3.3 K(+) channels influence the threshold for a form of burst discharge that has an established role in feature extraction of sensory input.