Affiliation:
1. Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520
Abstract
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 [Formula: see text] (constant pH 7.40) to the bath (basolateral) solution caused [Ca2+]i to increase from 57 ± 3 to 97 ± 9nM( 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 [Formula: see text] to the lumen. In 14 tubules in which we added [Formula: see text] 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 [Formula: see text] caused [Ca2+]i to rise by 62 ± 17 nM ( n = 10), whereas an OOE solution containing 0% CO2/22 mM [Formula: see text] caused only a trivial increase. Removing Ca2+ from the lumen and bath, or adding 10 μM nifedipine (L- and T-type Ca2+-channel blocker) or 2 μM thapsigargin [sarco-(endo) plasmic reticulum Ca2+-ATPase inhibitor] or 4 μM 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.
Publisher
American Physiological Society
Cited by
6 articles.
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