Differential Assembly of Inwardly Rectifying K+ Channel Subunits, Kir4.1 and Kir5.1, in Brain Astrocytes

Abstract

The inwardly rectifying K ؉ channel subunit Kir5.1 is expressed abundantly in the brain, but its precise distribution and function are still largely unknown. Because Kir5.1 is co-expressed with Kir4

Gene expression profiling of astrocytes from hyperammonemic mice reveals altered pathways for water and potassium homeostasis in vivo

“…The downregulation of Cx43 observed in FACS-purified GFAP-EGFP + astrocytes was analyzed further, because of: (i) the fundamental physiological role of Cx43 as the main gap junction channel in astrocytes (Dermietzel et al, 1991;Iacobas et al, 2004); (ii) the downregulation of Cx43 also found in cortical tissue of hyperammonemic mice (present study); (iii) the clustering and apparent loss of connectivity between EGFP + astrocytes along the brain vasculature of hyperammonemic animals (present study); and (iv) the importance of Cx43 for potassium homeostasis in the brain (Kozoriz et al, 2006;Wallraff et al, 2006). In addition to Cx43 and gap junctions, potassium homeostasis is also regulated by astrocytic inward-rectifying potassium channels, which exist as Kir4.1 homodimers and Kir4.1/Kir5.1 heterodimers (Hibino et al, 2004;Kofuji et al, 2002;Kucheryavykh et al, 2007;Neusch et al, 2006). In the mouse neocortex, the heteromeric Kir4.1/Kir5.1 channel was detected perivascularly, and both the homomeric Kir4.1 and heteromeric Kir4.1/Kir5.1 channel were found in perisynaptic astrocytic processes (Hibino et al, 2004).…”

“…In addition to Cx43 and gap junctions, potassium homeostasis is also regulated by astrocytic inward-rectifying potassium channels, which exist as Kir4.1 homodimers and Kir4.1/Kir5.1 heterodimers (Hibino et al, 2004;Kofuji et al, 2002;Kucheryavykh et al, 2007;Neusch et al, 2006). In the mouse neocortex, the heteromeric Kir4.1/Kir5.1 channel was detected perivascularly, and both the homomeric Kir4.1 and heteromeric Kir4.1/Kir5.1 channel were found in perisynaptic astrocytic processes (Hibino et al, 2004). Kir4.1 was also shown to be part of a plasma membrane dystroglycan complex that includes Aqp4 (Hibino et al, 2004;Kofuji and Newman, 2004), Agp4 the main astrocytic water channel at the brain vasculature and key to water homeostasis in brain (Badaut et al, 2002;Solenov et al, 2004).…”

“…In the mouse neocortex, the heteromeric Kir4.1/Kir5.1 channel was detected perivascularly, and both the homomeric Kir4.1 and heteromeric Kir4.1/Kir5.1 channel were found in perisynaptic astrocytic processes (Hibino et al, 2004). Kir4.1 was also shown to be part of a plasma membrane dystroglycan complex that includes Aqp4 (Hibino et al, 2004;Kofuji and Newman, 2004), Agp4 the main astrocytic water channel at the brain vasculature and key to water homeostasis in brain (Badaut et al, 2002;Solenov et al, 2004). Aqp4, Cx43, and Kir4.1/Kir5.1 colocalize to astrocytic end-feet at the cerebral microvasculature (Badaut et al, 2002;Hibino et al, 2004;Rouach et al, 2002) and are involved in the regulation of potassium and water homeostasis in the brain.…”

“…Kir4.1 was also shown to be part of a plasma membrane dystroglycan complex that includes Aqp4 (Hibino et al, 2004;Kofuji and Newman, 2004), Agp4 the main astrocytic water channel at the brain vasculature and key to water homeostasis in brain (Badaut et al, 2002;Solenov et al, 2004). Aqp4, Cx43, and Kir4.1/Kir5.1 colocalize to astrocytic end-feet at the cerebral microvasculature (Badaut et al, 2002;Hibino et al, 2004;Rouach et al, 2002) and are involved in the regulation of potassium and water homeostasis in the brain. The similarity in the expression response of these three channels to HA in vivo shown in the present study may reflect a functional association between Cx43, Kir5.1 and Aqp4.…”

“…Further evidence for a possible coupling of K + and water transport in perivascular astrocytes stems from the observation that Aqp4 and Kir4.1 channels are interconnected via a dystrophin-glycoprotein complex (DGC) at the plasma membrane (PM) of perivascular retinal glia cells (Connors and Kofuji, 2006) and astrocytes (Guadagno and Moukhles, 2004;Hibino et al, 2004;Kofuji and Newman, 2004). The co-localization of Kir4.1, and Aqp4 to one PM complex in astrocytic end-feet, at capillaries, and at the pia further supports the notion that the regulation of extracellular potassium levels is coupled with water transport (Hibino et al, 2004;Nagelhus et al, 2004).…”