Cell-Specific Expression of the IP3 Receptor Gene Family in the Kidney

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Abstract
Background/Aim: The localization of inositol trisphosphate (IP3) receptor isoforms, types 1–3, in the kidney and their role in the regulation of the intracellular calcium concentration – [Ca2+]i – are discussed. Methods: Immunohistological studies with isoform-specific antibodies were performed to reveal the localization of IP3 receptor isoforms. To examine the role of IP3 receptor type 1 in the glomeruli, the responses of [Ca2+]i to hormonal stimuli were examined in IP3 receptor type 1 knockout mice. Results: In the immunohistological study, type 1 receptor was present in arteries, afferent arterioles, and mesangial cells. Double staining with antibodies against aquaporin 2 and IP3 type 2 receptor revealed that type 2 receptor was localized mainly in the intercalated cells. The type 3 receptor showed characteristic intracellular localization in the collecting duct cells of the cortex to the outer medulla. Immunostaining of type 3 receptor was most intense in the cytoplasm on the basolateral membrane side and was not seen on the apical side. The responses of [Ca2+]i to angiotensin II and endothelin in the glomeruli were markedly attenuated in IP3 receptor type 1 knockout mice. Conclusions: The three isoforms of the IP3 receptor showed distinctive localization in the kidney, and the type 1 receptor plays a major role in the regulation of [Ca2+]i in the glomeruli. The physiological significance of the cell-specific localization, however, remains to be determined.