Differential Expression of Kir6.1 and SUR2B mRNAs in the Vasculature of Various Tissues in Rats

Abstract

ATP-sensitive K(+) channels (K(ATP)) couple the intermediary metabolism to cellular excitability and play an important role in the cardio-protective effect of ischemic preconditioning and the activity-dependent autoregulation of cerebral circulation. Although previous studies using PCR and Northern blot suggest that the vascular isoform may consist of Kir6.1 and SUR2B, their expression and precise distribution in various vasculatures remain unknown. To illustrate their vascular expression, we performed this study using in situ hybridization histochemistry. Antisense riboprobes were synthesized by in vitro transcription and labeled with digoxigenin. Distributions of these mRNAs in the various blood vessels were revealed under a bright-field microscope. The expression of Kir6.1 and SUR2B mRNAs was observed in small and intermediate arteries as well as arterioles in several tissues, including basilar, vertebral, mesenteric, coronary and renal arteries. The transcripts were found in arterial smooth muscles. Also, we observed Kir6.1/SUR2B expression in capillary beds. The Kir6.1 and SUR2B expression pattern showed clear overlap, suggesting that they may form heteromeric K(ATP) channels in these tissues. The Kir6.1 and SUR2B stains were detected in aorta and renal tubular cells although their expression level was extremely low. In contrast, the Kir6.1 and SUR2B mRNAs were not seen in vena cava, other small veins, myocardium and skeletal muscles. With their strong expression in small arteries and capillaries, it is very likely that the Kir6.1 and SUR2B form the vascular isoform of K(ATP) channels in these vasculatures.

ATP-sensitive K+ -channel Subunits on the Mitochondria and Endoplasmic Reticulum of Rat Cardiomyocytes

“…The expression of Kir6.1 protein in rat cardiomyocytes and coronary arteries was consistent with the wide distribution of Kir6.1 mRNA in rat heart (Inagaki et al 1995;Pountney et al 2001;van Bever et al 2004) and in the smooth muscle of blood vessels (Yamada et al 1997;Suzuki et al 2001;Miki et al 2002;Li et al 2003;Miura et al 2003). The subcellular localization of Kir6.1 in the mitochondria was also consistent with the results in isolated mitochondrial fraction analysis (Lacza et al 2003) and in isolated ventricular myocytes analysis by colocalized with mitochondrial marker MitoFluor red (Singh et al 2003).…”

KATPChannels in the Cardiovascular System

“…The tissue distributions of SUR2A and SUR2B are also distinct. SUR2A is expressed at high levels in cardiac ventricle [but not in the rodent atrium (18)], skeletal muscle, and ovary and at moderate levels in brain neurons, tongue, and pancreatic islets (18,371,932); SUR2B is more widely expressed, for example, in vascular smooth muscle, heart, cardiac specialized conduction system myocytes, vascular endothelium, lung epithelium, hair follicles, renal proximal tubules, renal tubular epithelial cells, microglia, astrocytes, and the dentate gyrus (48,50,86,144,439,491,496,626,637,705,734,906,907,932,933). The transcriptional mechanisms responsible for the differential tissue distributions of SUR2A and SUR2B remain to be elucidated.…”

Expression of inwardly rectifying potassium channel subunits in native human retinal pigment epithelium

“…The Kir6 tetrameric complex forms the channel's pore structure whereas the SUR (SUR1, SUR2A, or SUR2B) tetramer confers its nucleotide sensitivity and aspects of its pharmacology. Kir6.1 and SUR2B subunits form vascular K ATP channels (Li et al, 2003), which are activated by ATP and nucleotide diphosphates (Yamada et al, 1997). There is immunological evidence that Kir6.1 subunits may also contribute to mitochrondrial K ATP channels (Cuong et al, 2005;Singh et al, 2003), but this interpretation has been challenged (Foster et al, 2008).…”