{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T10:57:32Z","timestamp":1781953052859,"version":"3.54.5"},"reference-count":54,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T00:00:00Z","timestamp":1725494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH National Institute of Diabetes and Digestive and Kidney Diseases","award":["DK126330"],"award-info":[{"award-number":["DK126330"]}]},{"name":"NIH National Institute of Diabetes and Digestive and Kidney Diseases","award":["EY028580"],"award-info":[{"award-number":["EY028580"]}]},{"name":"NIH National Institute of Diabetes and Digestive and Kidney Diseases","award":["IK2BX004097"],"award-info":[{"award-number":["IK2BX004097"]}]},{"name":"University at Buffalo","award":["DK126330"],"award-info":[{"award-number":["DK126330"]}]},{"name":"University at Buffalo","award":["EY028580"],"award-info":[{"award-number":["EY028580"]}]},{"name":"University at Buffalo","award":["IK2BX004097"],"award-info":[{"award-number":["IK2BX004097"]}]},{"name":"NIH National Eye Institute","award":["DK126330"],"award-info":[{"award-number":["DK126330"]}]},{"name":"NIH National Eye Institute","award":["EY028580"],"award-info":[{"award-number":["EY028580"]}]},{"name":"NIH National Eye Institute","award":["IK2BX004097"],"award-info":[{"award-number":["IK2BX004097"]}]},{"DOI":"10.13039\/100000738","name":"US Department of Veterans Affairs","doi-asserted-by":"publisher","award":["DK126330"],"award-info":[{"award-number":["DK126330"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"US Department of Veterans Affairs","doi-asserted-by":"publisher","award":["EY028580"],"award-info":[{"award-number":["EY028580"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"US Department of Veterans Affairs","doi-asserted-by":"publisher","award":["IK2BX004097"],"award-info":[{"award-number":["IK2BX004097"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Congenital proximal renal tubular acidosis (pRTA) is a rare systemic disease caused by mutations in the SLC4A4 gene that encodes the electrogenic sodium bicarbonate cotransporter, NBCe1. The major NBCe1 protein variants are designated NBCe1-A, NBCe1-B, and NBCe1-C. NBCe1-A expression is kidney-specific, NBCe1-B is broadly expressed and is the only NBCe1 variant expressed in the heart, and NBCe1-C is a splice variant of NBCe1-B that is expressed in the brain. No cardiac manifestations have been reported from patients with pRTA, but studies in adult rats with virally induced reduction in cardiac NBCe1-B expression indicate that NBCe1-B loss leads to cardiac hypertrophy and prolonged QT intervals in rodents. NBCe1-null mice die shortly after weaning, so the consequence of congenital, global NBCe1 loss on the heart is unknown. To circumvent this issue, we characterized the cardiac function of NBCe1-B\/C-null (KOb\/c) mice that survive up to 2 months of age and which, due to the uninterrupted expression of NBCe1-A, do not exhibit the confounding acidemia of the globally null mice. In contrast to the viral knockdown model, cardiac hypertrophy was not present in KOb\/c mice as assessed by heart-weight-to-body-weight ratios and cardiomyocyte cross-sectional area. However, echocardiographic analysis revealed reduced left ventricular ejection fraction, and intraventricular pressure\u2013volume measurements demonstrated reduced load-independent contractility. We also observed increased QT length variation in KOb\/c mice. Finally, using the calcium indicator Fura-2 AM, we observed a significant reduction in the amplitude of Ca2+ transients in paced KOb\/c cardiomyocytes. These data indicate that congenital, global absence of NBCe1-B\/C leads to impaired cardiac contractility and increased QT length variation in juvenile mice. It remains to be determined whether the cardiac phenotype in KOb\/c mice is influenced by the absence of NBCe1-B\/C from neuronal and endocrine tissues.<\/jats:p>","DOI":"10.3390\/ijms25179610","type":"journal-article","created":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T02:34:06Z","timestamp":1725503646000},"page":"9610","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Left Ventricular Systolic Dysfunction in NBCe1-B\/C-Knockout Mice"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4778-9187","authenticated-orcid":false,"given":"Clayton T.","family":"Brady","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics, Jacobs School of Medicine and Biomedical Sciences, State University of New York: The University at Buffalo, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aniko","family":"Marshall","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Jacobs School of Medicine and Biomedical Sciences, State University of New York: The University at Buffalo, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa A.","family":"Eagler","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine and the Clinical and Translational Research Center, State University of New York: University at Buffalo, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Pon","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine and the Clinical and Translational Research Center, State University of New York: University at Buffalo, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E.","family":"Duffey","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Jacobs School of Medicine and Biomedical Sciences, State University of New York: The University at Buffalo, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8832-6771","authenticated-orcid":false,"given":"Brian R.","family":"Weil","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Jacobs School of Medicine and Biomedical Sciences, State University of New York: The University at Buffalo, Buffalo, NY 14203, USA"},{"name":"Division of Cardiovascular Medicine and the Clinical and Translational Research Center, State University of New York: University at Buffalo, Buffalo, NY 14203, USA"},{"name":"Veterans Affairs Western New York Health Care System, Buffalo, NY 14215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6221-8625","authenticated-orcid":false,"given":"Jennifer K.","family":"Lang","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine and the Clinical and Translational Research Center, State University of New York: University at Buffalo, Buffalo, NY 14203, USA"},{"name":"Veterans Affairs Western New York Health Care System, Buffalo, NY 14215, USA"},{"name":"Department of Biomedical Engineering, State University of New York: University at Buffalo, Buffalo, NY 14260, USA"},{"name":"Department of Pharmacology and Toxicology, State University of New York: University at Buffalo, Buffalo, NY 14203, USA"},{"name":"Department of Medicine, State University of New York: University at Buffalo, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark D.","family":"Parker","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Jacobs School of Medicine and Biomedical Sciences, State University of New York: The University at Buffalo, Buffalo, NY 14203, USA"},{"name":"Department of Ophthalmology, Jacobs School of Medicine and Biomedical Sciences, State University of New York: The University at Buffalo, Buffalo, NY 14209, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Liu, Y., Sheng, W., Wu, J., Zheng, J., Zhi, X., Zhang, S., Gu, C., Guo, D., and Wang, W. 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