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: Furosemide and ATP both cause significant intracellular alkalizations in mTAL that require NHE3 activity (this study and de Bruijn et al. 2013), and they are known to reduce tubular transport in this segment (Greger 1985, Marques et al. 2012). It was therefore interesting to study whether the pHi effects of the two substances are additive. Figure6a illustrates that furosemide causes a marked intracellular alkalization from pH 7.25 ± 0.08 to pH 7.60 ± 0.02 (n = 6, Fig.6b). When basolateral ATP (100 μm) was added during the continuous presence of luminal furosemide, pHi remained unchanged. These results do not support an additive effect of these two alkalizing stimuli and thus are consistent with the notion of a common underlying cause.
Affiliation: Department of Biomedicine, Physiology and Biophysics, Aarhus University, Aarhus C, Denmark.