P2X receptors trigger intracellular alkalization in isolated perfused mouse medullary thick ascending limb.
Bottom Line: The renal outer medullary K(+) channel (ROMK) is sensitive to intracellular pH where a reduction leads to closing of ROMK.We speculated that P2X receptor stimulation in the TAL could lead to changes in pHi , leading to a reduction in NaCl transport.Typically, Gq -coupled receptors cause a significant acidification of tubular epithelial cells, which was confirmed in this study, by P2Y2 and Ca(2+) sensing receptor stimulation.
Affiliation: Department of Biomedicine, Physiology and Biophysics, Aarhus University, Aarhus C, Denmark.Show MeSH
Mentions: Figure1a shows a typical pHi recording of a perfused mTAL. Under resting conditions, the pHi of this tubule was 7.28. The average pHi of the summarized data from all perfused mTALs was 7.31 ± 0.05 (n = 14, Fig.1b). Application of basolateral ATP (100 μm) caused a reversible intracellular alkalization in perfused mTAL, which was sustained during the 2-min exposure to ATP and then returned to the basal pHi after a washout period of 2–5 min. The average pHi during ATP exposure was 7.45 ± 0.06, and after 5-min washout, the pHi recovered to 7.31 ± 0.05 (Fig.1b, P < 0.0001). These data reflect that ATP causes an intracellular alkalization with a magnitude of 0.14 ± 0.02 pH units. Figure2 shows the concentration–response curve of ATP in a range from 100 nm to 500 μm. The estimated EC50 was 6.74 ± 1.67 μm. Interestingly, low concentrations of ATP (1 μm) resulted in a decrease in pHi, suggesting that basolateral ATP has a dual effect on intracellular pH in mouse mTAL.
Affiliation: Department of Biomedicine, Physiology and Biophysics, Aarhus University, Aarhus C, Denmark.