Limits...
P2X receptors trigger intracellular alkalization in isolated perfused mouse medullary thick ascending limb.

de Bruijn PI, Bleich M, Praetorius HA, Leipziger J - Acta Physiol (Oxf) (2014)

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.This increased NHE3 activity causes H(+) secretion in the mTAL and provides further support that the TAL is a site of urinary acidification.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedicine, Physiology and Biophysics, Aarhus University, Aarhus C, Denmark.

Show MeSH

Related in: MedlinePlus

P2X receptor antagonist oxidized ATP (oATP) inhibits the ATP-induced alkalization. (a+b) Original trace and summary (ΔpHi) of time control experiments, where a perfused medullary thick ascending limb is exposed to basolateral ATP twice with a 12-min washout period in between. (c+d) Original trace and summary (ΔpHi) of experiments, where pre-incubation with oATP (50 μm, 5-min exposure) completely inhibits the ATP-induced alkalization. *Indicates statistical significance P < 0.01, n = 6.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4374443&req=5

fig04: P2X receptor antagonist oxidized ATP (oATP) inhibits the ATP-induced alkalization. (a+b) Original trace and summary (ΔpHi) of time control experiments, where a perfused medullary thick ascending limb is exposed to basolateral ATP twice with a 12-min washout period in between. (c+d) Original trace and summary (ΔpHi) of experiments, where pre-incubation with oATP (50 μm, 5-min exposure) completely inhibits the ATP-induced alkalization. *Indicates statistical significance P < 0.01, n = 6.

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.


P2X receptors trigger intracellular alkalization in isolated perfused mouse medullary thick ascending limb.

de Bruijn PI, Bleich M, Praetorius HA, Leipziger J - Acta Physiol (Oxf) (2014)

P2X receptor antagonist oxidized ATP (oATP) inhibits the ATP-induced alkalization. (a+b) Original trace and summary (ΔpHi) of time control experiments, where a perfused medullary thick ascending limb is exposed to basolateral ATP twice with a 12-min washout period in between. (c+d) Original trace and summary (ΔpHi) of experiments, where pre-incubation with oATP (50 μm, 5-min exposure) completely inhibits the ATP-induced alkalization. *Indicates statistical significance P < 0.01, n = 6.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4374443&req=5

fig04: P2X receptor antagonist oxidized ATP (oATP) inhibits the ATP-induced alkalization. (a+b) Original trace and summary (ΔpHi) of time control experiments, where a perfused medullary thick ascending limb is exposed to basolateral ATP twice with a 12-min washout period in between. (c+d) Original trace and summary (ΔpHi) of experiments, where pre-incubation with oATP (50 μm, 5-min exposure) completely inhibits the ATP-induced alkalization. *Indicates statistical significance P < 0.01, n = 6.
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.

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.This increased NHE3 activity causes H(+) secretion in the mTAL and provides further support that the TAL is a site of urinary acidification.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedicine, Physiology and Biophysics, Aarhus University, Aarhus C, Denmark.

Show MeSH
Related in: MedlinePlus