Localization of the Na⁺‐activated K⁺ channel Slick in the rat central nervous system

Abstract

Na+-activated K+ currents (K(Na)) have been reported in multiple neuronal nuclei and the properties of K(Na) vary in different cell types. We have described previously the distribution of Slack, a Na+-activated K+ channel subunit. Another recently cloned Na+-activated K+ channel is Slick, which differs from Slack in its rapid activation and its sensitivity to intracellular ATP levels. We now report the localization of Slick in the rat central nervous system using in situ and immunohistochemical techniques. As for Slack, we find that Slick is widely distributed in the brain. Specifically, strong hybridization signals and immunoreactivity were found in the brainstem, including auditory neurons such as the medial nucleus of the trapezoid body. As has also been shown for Slack, Slick is expressed in the olfactory bulb, red nucleus, facial nucleus, pontine nucleus, oculomotor nucleus, substantia nigra, deep cerebellar nuclei, vestibular nucleus, and the thalamus. Slick mRNA and protein, however, also are found in certain neurons that do not express Slack. These neurons include those of the hippocampal CA1, CA2, and CA3 regions, the dentate gyrus, supraoptic nucleus, hypothalamus, and cortical layers II, III, and V. These data suggest that Slick may function independently of Slack in these regions. Computer simulations indicate that Slick currents can cause adaptation during prolonged stimuli. Such adaptation allows a neuron to respond to high-frequency stimulation with lower-frequency firing that remains temporally locked to individual stimuli, a property seen in many auditory neurons. Although it is not yet known if Slick and Slack subunits heteromultimerize, the existence of two genes that encode K(Na), that are widely expressed in the nervous system, with both overlapping and nonoverlapping distributions, provides the basis for the reported heterogeneity in the properties of K(Na) from various neurons.

Sparse But Highly Efficient Kv3 Outpace BKCaChannels in Action Potential Repolarization at Hippocampal Mossy Fiber Boutons

“…The isolated sodium current and the inward current component of the combined Na ϩ and K ϩ current did not differ, either ( p Ͼ 0.15 for half-duration, rise time, and peak current amplitude). The lack of electrophysiological evidence for K Na -mediated currents in rat hippocampal MFBs is consistent with immunohistochemical studies on Slick (Slo2.1) and Slack (Slo2.2) (Bhattacharjee et al, 2002(Bhattacharjee et al, , 2005, which did not show positive antibody staining in the mossy fiber tract of rat hippocampus.…”

Opposite Regulation of Slick and Slack K+Channels by Neuromodulators

“…In hippocampus, the Slick (Slo2.1) channel is expressed in both CA1 and CA3 regions, in which it colocalizes with the mAChR1 receptor (Fig. 8C,D) (Levey et al, 1995;Bhattacharjee et al, 2005). Finally, mGluR1 receptors are expressed in hippocampus (Shigemoto et al, 1997).…”

“…The goal of these colabeling experiments was to verify that both receptors and channels could be expressed in the same types of identified cells. Both Slo2.1 and Slo2.2 are very widely expressed throughout the CNS (Bhattacharjee et al, 2002(Bhattacharjee et al, , 2005. Figure 8 shows some examples of colocalization.…”

Na + -mediated coupling between AMPA receptors and K Na channels shapes synaptic transmission

“…Na ϩ -activated K ϩ channels (K Na ) have been shown to exist in many types of neurons (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). They are encoded for by two genes, Slick (Slo 2.1) and Slack (Slo 2.2) (11)(12)(13), and display a wide distribution in many regions in the brain (12,14,15). Most of the information available on these channels is related to their activation by Na ϩ influx through voltage-gated channels, but it has been difficult to assess their physiological role.…”