Localization of the Sulphonylurea Receptor Subunits, SUR2A and SUR2B, in Rat Renal Tubular Epithelium

Abstract

ATP-sensitive K + (K ATP ) channels in the kidney are considered to play roles in regulating membrane potential according to changes in the intracellular ATP concentration. They are composed of two types of subunits; the pore subunits (Kir6.1, Kir6.2), which are members of the inwardly rectifying K + channel family, and the regulatory subunits, the sulphonylurea receptors, which belong to the ATP-binding cassette (ABC) superfamily. The sulphonylurea receptors (SURs) are receptors of sulphonylureas widely used for the treatment of type 2 diabetes mellitus. The SURs are divided into two isoforms, SUR1 and SUR2, the latter was further divided into SUR2A and SUR2B. In the present study, we have investigated the mRNA expression by RT-PCR assay, and protein expression profi les by immunoblotting, immunohistochemistry, and immunoelectron microscopy with anti SUR2A and anti SUR2B antibodies. RT-PCR detected the presence of mRNA transcripts of the SUR2A and SUR2B, while SUR1 mRNA was barely detected. In immunoblotting, SUR2A protein was detected distinctly in the microsomal fraction, weakly in the mitochondrial fraction and at negligible level in the cell membrane fraction. In contrast, the SUR2B protein was detected intensely in the microsomal fraction, with a low level in the mitochondrial fraction and scarcely in the cell membrane fraction. In immunohistochemistry SUR2A and SUR2B proteins were widely distributed in renal tubular epithelial cells, glomerular mesangial cells, and the endothelium and the smooth muscle of blood vessels. In immunoelectron microscopy, the immunoreactivity was localized in the endoplasmic reticulum and mitochondria throughout the epithelial cells for SUR2A, and dominantly in the apical cytoplasm of the cells for SUR2B. In conclusion, the regulatory subunits of the K ATP channel in the rat kidney are SUR2A and SUR2B; they also are candidate regulatory subunits for the mitochondrial K ATP channel.ATP-sensitive K + channel; sulphonylurea receptor; immunohistochemistry; immunoelectron microscopy; kidney.Tohoku

Nicorandil as a novel therapy for advanced diabetic nephropathy in the eNOS-deficient mouse

“…While nicorandil has a dual function in which it is able to donate NO and stimulate the ATP-dependent K channel, the protective effect on podocytes is likely through opening of ATP-dependent K channels (37) because a cGMP signal, as a second messenger of NO, was not detected in the glomerulus. With respect to the localization of SUR-2 in the kidney, Zhou et al (38) found that SUR-2 is expressed in tubular epithelial cells, yet their finding is distinct from our results. However, such discrepancy could be explained by the difference in species or antibody used.…”

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.…”

Different sulfonylureas induce the apoptosis of proximal tubular epithelial cell differently via closing KATP channel

“…SURs are present in a wide variety of extra-pancreatic tissues (Gribble & Reimann, 2003). Investigations indicated that SUR2, one common subtype of SUR, is located in PTECs (Zhou et al 2008; Szamosfalvi et al 2002). Hence, it is conceivable that SUs could act directly on the PTECs.…”