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
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Mentions: We previously demonstrated that P2X1, P2X4 and P2X5 receptors are expressed in TAL of mice (Marques et al. 2012). To confirm that the ATP-induced alkalization is mediated by P2X receptor stimulation, we used the unspecific irreversible P2X receptor antagonist oATP. Figure4a shows an original trace of a time control experiment, for two consecutive applications of basolateral ATP to a perfused mTAL separated by 12-min washout. It is clear from both Figure4a and the summarized data in Figure4b that ATP induced an alkalization of comparable size in both cases. When, however, ATP was applied after the irreversible P2X receptor antagonist oATP (50 μm), the ATP-induced alkalization was completely abolished (Fig.4c). Instead, an acidification was observed, congruent with a residual P2Y2 receptor stimulation (Fig.4d). Thus, the ATP-induced alkalization is mediated through basolateral P2X receptors.
Affiliation: Department of Biomedicine, Physiology and Biophysics, Aarhus University, Aarhus C, Denmark.