G-protein-gated inward rectifier K+ channel proteins (GIRK1) are present in the soma and dendrites as well as in nerve terminals of specific neurons in the brain

Abstract

G-protein-gated inward rectifier potassium (GIRK) channels are coupled to numerous neurotransmitter receptors in the brain and can play important roles in modulating neuronal function, depending on their localization in a given neuron. Site-directed antibodies to the extreme C terminus of GIRK1 (or KGA1), a recently cloned component of GIRK channels, have been used to determine the relative expression levels and distribution of the protein in different regions of the rat brain by immunoblot and immunohistochemical techniques. We report that the GIRK1 protein is expressed prominently in the olfactory bulb, hippocampus, dentate gyrus, neocortex, thalamus, cerebellar cortex, and several brain stem nuclei. In addition to the expected localization in somas and dendrites, where GIRK channels may mediate postsynaptic inhibition, GIRK1 proteins were also found in axons and their terminal fields, suggesting that GIRK channels can also modulate presynaptic events. Furthermore, the distribution of the protein to either somatodendritic or axonal-terminal regions of neurons varied in different brain regions, which would imply distinct functions of these channels in different neuronal populations. Particularly prominent staining of the cortical barrels of layer IV of the neocortex, and the absence of this staining with unilateral kainate lesions of the thalamus, suggest that the GIRK1 protein is expressed in thalamocortical nerve terminals in which GIRK channels may mediate the actions of mu opiate receptors.

Characterization of Rebound Depolarization in Neurons of the Rat Medial Geniculate Body In Vitro

“…There is a high level of expression of GIRK channels, which are one of the subfamilies of Kir channels, in MGB neurons [52][53][54]. Activation of GIRK channels using the GABA B receptor agonist baclofen suppressed RD (Fig.…”

GIRK1 immunoreactivity is present predominantly in dendrites, dendritic spines, and somata in the CA1 region of the hippocampus

“…moleculare of the dentate gyrus. Together, these in situ and immunocytochemical data strongly suggest that GIRK1-IR may be located in the dendrites of pyramidal and granule cells (18,19). Alternatively, this labeling may be attributable to the presence of GIRK1 in terminal fields of afferents to the hippocampal formation (e.g., from the entorhinal cortex and thalamus).…”

“…Alternatively, this labeling may be attributable to the presence of GIRK1 in terminal fields of afferents to the hippocampal formation (e.g., from the entorhinal cortex and thalamus). The latter suggestion was supported by immunolabeling of hippocampal cultures, which failed to demonstrate the localization of GIRK1-IR in pyramidal cell dendrites (18) and also by a recent study showing decreases in GIRK1-IR following lesions of the thalamus (19). Therefore, the aim of the present study was to determine the subcellular distribution of GIRK1-IR in the CA1 region of the rat hippocampus using electron microscopy with a previously characterized anti-peptide antibody directed against the carboxyl-terminal tail of GIRK1 (18).…”

“…One member of this family, GIRK1, has been previously localized throughout the brain using both in situ hybridization (17) and light microscopic immunocytochemistry (18,19). We chose the hippocampus for further anatomical localization, because extensive anatomical and physiological studies previously performed in this brain region make it a useful model for studying GIRK-mediated functions.…”

“…Although high levels of GIRK1 mRNA were found in the principal cells of the hippocampal formation (i.e., the pyramidal and granule cells; refs. 17 and 20), light microscopic studies showed that the somata of these neurons contained weak (19) or no significant (18) GIRK1-immunoreactivity (IR). In contrast, higher levels of diffuse GIRK1-IR were seen in fields that contain the dendrites of pyramidal and granule cells: stratum (str.)…”