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Bouyer P, Zhou Y, Boron WF: An increase in intracellular calcium concentration that is induced by basolateral CO2 in rabbit renal proximal tubule. Am J Physiol Renal Physiol. 2003 Oct;285(4):F674-87. Epub 2003 Jun 17.
Working with isolated perfused S2 proximal tubules, we asked whether the basolateral CO2 sensor acts, in part, by raising intracellular Ca2+ concentration ([Ca2+] i), monitored with the dye fura 2 (or fura-PE3). In paired experiments, adding 5% CO2/22 mM HCO3- (constant pH 7.40) to the bath (basolateral) solution caused [Ca2+] i to increase from 57 +/- 3 to 97 +/- 9 nM (n = 8, P < 0.002), whereas the same maneuver in the lumen had no effect. Intracellular pH (pHi), measured with the dye BCECF, fell by 0.54 +/- 0.08 (n = 14) when we added CO2/HCO3- to the lumen. In 14 tubules in which we added CO2/HCO3- to the bath, pHi fell by 0.55 +/- 0.11 in 9 with a high initial pHi, but rose by 0.28 +/- 0.07 in the other 5 with a low initial pHi. Thus it cannot be a pHi change that triggers the [Ca2+] i increase. Introducing to the bath an out-of-equilibrium (OOE) solution containing 20% CO2/no HCO3-/pH 7.40 caused [Ca2+] i to rise by 62 +/- 17 nM (n = 10), whereas an OOE solution containing 0% CO2/22 mM HCO3-/pH 7.40 caused only a trivial increase. Removing Ca2+ from the lumen and bath, or adding 10 microM nifedipine (L- and T-type Ca2+-channel blocker) or 2 microM thapsigargin [sarco-(endo) plasmic reticulum Ca2+-ATPase inhibitor] or 4 microM rotenone (mitochondrial inhibitor) to the lumen and bath, failed to reduce the CO2-induced increase in [Ca2+] i. Adding 10 mM caffeine (ryanodine-receptor agonist) had no effect on [Ca2+] i. Thus basolateral CO2, presumably via a basolateral sensor, triggers the release of Ca2+ from a nonconventional intracellular pool. |
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