Characteristics of spontaneous calcium oscillations in renal tubular epithelial cells

Abstract

The kidney is a major organ involved in calcium (Ca(2+)) metabolism. Ca(2+) is transported through renal tubular epithelial cells. The intracellular free calcium concentration ([Ca(2+)](i)) is tightly controlled at a low concentration, but transient increases and oscillations in [Ca(2+)](i) are induced by various conditions. In this study, we investigated the mechanisms underlying the spontaneous [Ca(2+)](i) oscillations observed in MDCK cells. [Ca(2+)](i) was monitored in fura-2-loaded Madin-Darby canine kidney (MDCK) cells using a calcium imaging system. We investigated the mechanism by which [Ca(2+)](i) changed by applying drugs or by changing the extracellular Ca(2+) concentration. Spontaneous [Ca(2+)](i) oscillations occurred in MDCK cells. The oscillations occurred irregularly and were not transmitted to neighboring cells. Spontaneous [Ca(2+)](i) oscillations in MDCK cells were initiated by Ca(2+) release from ryanodine/IP(3)-sensitive intracellular calcium stores, and their frequency was largely unaffected by the extracellular Ca(2+) concentration. Moreover, the frequency of the oscillations was increased by extracellular nucleotide, but was decreased when the nucleotides were removed. Our study suggested that [Ca(2+)](i) release from ryanodine/IP(3)-sensitive intracellular calcium stores mediates spontaneous [Ca(2+)](i) oscillations in MDCK cells. Calcium oscillations may be associated with the function of the renal tubular epithelial cells.