Evidence for a regulated Ca2+ entry in proximal tubular cells and its implication in calcium stone formation

• Autores: Ibeh, Cliff Lawrence; Yiu, Allen J.; Kanaras, Yianni L.; Paal, Edina; Birnbaumer, Lutz; Jose, Pedro A.; Bandyopadhyay, Bidhan C.
• Año de publicación: 2019
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Journal of Cell Science. 2019, 132
• Materia: NEFROLOGIA; UROLITIASIS; CALCIO; RIÑON; MEDICINA
• Institución: Pontificia Universidad Católica Argentina

Fil: Ibeh, Cliff-Lawrence. Veterans Affairs Medical Center. Research Service Center. Calcium Signaling Laboratory; Estados Unidos
Fil: Yiu, Allen J. Veterans Affairs Medical Center. Research Service Center. Calcium Signaling Laboratory; Estados Unidos
Fil: Yiu, Allen J. The George Washington University. Division of Renal Diseases & Hypertension. Department of Medicine; Estados Unidos
Fil: Kanaras, Yianni L. Veterans Affairs Medical Center. Research Service Center. Calcium Signaling Laboratory; Estados Unidos
Fil: Paal, Edina. Veterans Affairs Medical Center. Pathology and Laboratory Service; Estados Unidos
Fil: Birnbaumer, Lutz. Research Triangle Park. National Institute of Environmental Health Sciences. Division of Intramural Research; Estados Unidos
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Jose, Pedro A. The George Washington University. Division of Renal Diseases & Hypertension. Department of Medicine; Estados Unidos
Fil: Jose, Pedro A. The George Washington University. Department of Pharmacology and Physiology; Estados Unidos
Fil: Bandyopadhyay, Bidhan C. Veterans Affairs Medical Center. Research Service Center. Calcium Signaling Laboratory; Estados Unidos
Fil: Bandyopadhyay, Bidhan C. The George Washington University. Division of Renal Diseases & Hypertension. Department of Medicine; Estados Unidos
Fil: Bandyopadhyay, Bidhan C. The George Washington University. Department of Pharmacology and Physiology; Estados Unidos
Abstract: Calcium phosphate (CaP) crystals, which begin to form in the early segments of the loop of Henle (LOH), are known to act as precursors for calcium stone formation. The proximal tubule (PT), which is just upstream of the LOH and is a major site for Ca2+ reabsorption, could be a regulator of such CaP crystal formation. However, PT Ca2+ reabsorption is mostly described as being paracellular. Here, we show the existence of a regulated transcellular Ca2+ entry pathway in luminal membrane PT cells induced by Ca2+-sensing receptor (CSR, also known as CASR)-mediated activation of transient receptor potential canonical 3 (TRPC3) channels. In support of this idea, we found that both CSR and TRPC3 are physically and functionally coupled at the luminal membrane of PT cells. More importantly, TRPC3-deficient mice presented with a deficiency in PT Ca2+ entry/transport, elevated urinary [Ca2+], microcalcifications in LOH and urine microcrystals formations. Taken together, these data suggest that a signaling complex comprising CSR and TRPC3 exists in the PT and can mediate transcellular Ca2+ transport, which could be critical in maintaining the PT luminal [Ca2+] to mitigate formation of the CaP crystals in LOH and subsequent formation of calcium stones.