دورية أكاديمية
Kcnma1 alternative splicing in mouse kidney: regulation during development and by dietary K + intake.
| العنوان: | Kcnma1 alternative splicing in mouse kidney: regulation during development and by dietary K + intake. |
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| المؤلفون: | Whelan SCM; Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States., Mutchler SM; Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States., Han A; Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States., Priestley C; Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States., Satlin LM; Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York, United States., Kleyman TR; Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.; Department of Cell Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States., Shi S; Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States. |
| المصدر: | American journal of physiology. Renal physiology [Am J Physiol Renal Physiol] 2024 Jul 01; Vol. 327 (1), pp. F49-F60. Date of Electronic Publication: 2024 May 23. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901990 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-1466 (Electronic) Linking ISSN: 15221466 NLM ISO Abbreviation: Am J Physiol Renal Physiol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Bethesda, Md. : American Physiological Society, c1997- |
| مواضيع طبية MeSH: | Alternative Splicing* , Large-Conductance Calcium-Activated Potassium Channel alpha Subunits*/genetics , Large-Conductance Calcium-Activated Potassium Channel alpha Subunits*/metabolism , Potassium, Dietary*/metabolism , Kidney*/metabolism, Animals ; Mice, Inbred C57BL ; Mice ; Male ; Gene Expression Regulation, Developmental ; Exons ; Female |
| مستخلص: | The pore-forming α-subunit of the large-conductance K + (BK) channel is encoded by a single gene, KCNMA1. BK channel-mediated K + secretion in the kidney is crucial for overall renal K + homeostasis in both physiological and pathological conditions. BK channels achieve phenotypic diversity by various mechanisms, including substantial exon rearrangements at seven major alternative splicing sites. However, KCNMA1 alternative splicing in the kidney has not been characterized. The present study aims to identify the major splice variants of mouse Kcnma1 in whole kidney and distal nephron segments. We designed primers that specifically cross exons within each alternative splice site of mouse Kcnma1 and performed real-time quantitative RT-PCR (RT-qPCR) to quantify relative abundance of each splice variant. Our data suggest that Kcnma1 splice variants within mouse kidney are less diverse than in the brain. During postnatal kidney development, most Kcnma1 splice variants at site 5 and the COOH terminus increase in abundance over time. Within the kidney, the regulation of Kcnma1 alternative exon splicing within these two sites by dietary K + loading is both site and sex specific. In microdissected distal tubules, the Kcnma1 alternative splicing profile, as well as its regulation by dietary K + , are distinctly different than in the whole kidney, suggesting segment and/or cell type specificity in Kcnma1 splicing events. Overall, our data provide evidence that Kcnma1 alternative splicing is regulated during postnatal development and may serve as an important adaptive mechanism to dietary K + loading in mouse kidney. NEW & NOTEWORTHY We identified the major Kcnma1 splice variants that are specifically expressed in the whole mouse kidney or aldosterone-sensitive distal nephron segments. Our data suggest that Kcnma1 alternative splicing is developmentally regulated and subject to changes in dietary K + . |
| معلومات مُعتمدة: | DK137329 HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); DK130901 HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); U54 DK137329 United States DK NIDDK NIH HHS; R01 DK130901 United States DK NIDDK NIH HHS; HL128053 HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); HL158295 HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI); DK038470 HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); R01 DK111380 United States DK NIDDK NIH HHS; DK129285 HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); R01 DK038470 United States DK NIDDK NIH HHS; T32 DK061296 United States DK NIDDK NIH HHS; R01 HL128053 United States HL NHLBI NIH HHS; T32 DK007052 United States DK NIDDK NIH HHS; DK111380 HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); DK061296 HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); DK007052 HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); R01 DK129285 United States DK NIDDK NIH HHS |
| فهرسة مساهمة: | Keywords: BK channel; Kcnma1; kidney; potassium; splice variants |
| المشرفين على المادة: | 0 (Large-Conductance Calcium-Activated Potassium Channel alpha Subunits) 0 (Kcnma1 protein, mouse) 0 (Potassium, Dietary) |
| تواريخ الأحداث: | Date Created: 20240523 Date Completed: 20240620 Latest Revision: 20240710 |
| رمز التحديث: | 20240710 |
| DOI: | 10.1152/ajprenal.00100.2024 |
| PMID: | 38779757 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1522-1466 |
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| DOI: | 10.1152/ajprenal.00100.2024 |