Cellular and subcellular localization of Kir2.1 subunits in neurons and glia in piriform cortex with implications for K⁺ spatial buffering

Abstract

Potassium channels of the Kir2 family are widely expressed in neurons and glia, where they form strong inwardly rectifying channels. Existing functional hypotheses for these channels in neurons are based on the weak outward conductance, whereas the leading hypothesis for glia, that they promote potassium spatial buffering, is based on inward conductance. Although the spatial buffering hypothesis has been confirmed for Müller glia in retina, many aspects of Kir2 channels that will be required for understanding their functional roles in neurons and other forms of glia have received little or no study. Particularly striking is the paucity of data regarding their cellular and subcellular localization. We address this gap for Kir2.1-containing channels by using light and electron microscopic immunocytochemistry. The analysis was of piriform cortex, a highly epileptogenic area of cerebral cortex, where pyramidal cells have K(+)-selective strong inward rectification like that observed in Müller cells, where Kir2.1 is the dominant Kir2 subunit. Pyramidal cells in adult piriform cortex also lack I(h), the mixed Na(+)-K(+) current that mediates a slower form of strong inward rectification in large pyramidal cells in neocortex and hippocampus. The experiments demonstrated surface expression of Kir2.1-containing channels in astrocytes and in multiple populations of pyramidal and nonpyramidal cells. Findings for astrocytes were not consistent with predictions for K(+) spatial buffering over substantial distance. However, findings for pyramidal cells suggest that they could be a conduit for spatially buffering K(+) when it is highly elevated during seizure.

Membrane and synaptic properties of pyramidal neurons in the anterior olfactory nucleus

“…Pyramidal neurons in the neocortex and hippocampus have a large I h , particularly in dendrites where I h is thought to normalize or scale synaptic inputs (Williams and Stuart 2000). Although it has been reported that piriform pyramidal neurons do not express I h (e.g., Howe et al 2008), we observed small, but consistent sags in AON, piriform, and pEN neurons, most likely resulting from I h . A small I h , as well as the results of our passive cable analysis, is consistent with a more passive and compact dendritic tree in piriform pyramidal neurons compared with neocortex (Bathellier et al 2009;Spruston 2008).…”

“…pEN principal neurons had a pronounced inward rectification, consistent with a higher expression of IRK and/or GIRK channels. In olfactory cortex, neurons, rather than glia, may buffer extracellular potassium, during local increases in extracellular potassium such as seizures (Howe et al 2008). Therefore, a high potassium buffering capacity of pEN neurons could be important in controlling excitation.…”

Expressional Analysis of Inwardly Rectifying Kir4.1 Channels in Groggy Rats, a Rat Model of Absence Seizures

“…In addition, absence seizures also negligibly affected the expression of Kir2.1, which even at low levels is also expressed in the astrocytes of several brain regions (e.g. piriform cortex and olfactory bulb) (26,27).…”

“…The expressional level of the Kir2.1 subunit was evaluated since Kir2.1 channels are also known to be expressed in astrocytes even at low density (26,27).…”

Aberrant Subcellular Dynamics of Sigma-1 Receptor Mutants Underlying Neuromuscular Diseases

“…K ir 2.1 homotetramers form an inwardly-rectifying K 1 channel (Yang et al, 1995;Collins et al, 1997;Hibino et al, 2010) that is widely expressed throughout the central nervous system (Bredt et al, 1995;Horio et al, 1996;Howe et al, 2008), as well as in cardiac, smooth, and striated myocytes (de Boer et al, 2010;Hibino et al, 2010). Genetic knockout of K ir 2.1 in mice results in death 8-12 hours after birth (Zaritsky et al, 2000); conversely, overexpression of K ir 2.1 leads to a 10-mV hyperpolarization in neuronal resting membrane potential and suppressed neuronal firing (Burrone et al, 2002;Béïque et al, 2011).…”