Abstract
To expel the excess protons generated during a cellular acidification and to fully recover basal intracellular pH (pH(i)), cardiac cells rely on the amiloride-sensitive Na/H antiport. We report that rat single ventricular cardiomyocytes, loaded with the fluorescent pH indicator Snarf-1 and treated with inhibitors of the Na/H antiport, amiloride or its analogues, partially restored their pH(i) through a bicarbonate-dependent mechanism following an acidosis (imposed by the ammonia-pulse technique). In the presence of ethylisopropylamiloride (10 μM) or amiloride (1 mM) and 25 mM bicarbonate in the extracellular solution, the average time that cells needed to recover half of their pH(i), following the removal of 20 mM NH4Cl, was 3.4 min, while the rate of proton efflux was calculated to be 2.0 mM/min. The stilbene derivative, 4-4'-di-isothiocyanostilbene-2,2'-disulphonate (DIDS 200 μM), a known blocker of anion transporters, inhibited this recovery. Both phenylephrine (100 μM, 3 μM propranolol present), an α1-adrenoceptor agonist, and ATP (10 μM), a purinergic agonist, significantly enhanced the rate of proton efflux that was due to this HCO3-dependent alkalinizing mechanism. Phenylephrine and ATP also shortened by three-fold the time that a myocyte needed to recover half of its initial pH(i). This bicarbonate-dependent alkalinizing mechanism could provide an additional means by which cardiac cells recover their pH(i) from acidosis, especially under conditions in which the Na/H antiport is inhibited. Furthermore, catecholamines and ATP, which are released under various pathophysiological conditions often associated with intracellular acidosis, could play an important role in the modulation of pH(i) under these conditions.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 597-600 |
| Number of pages | 4 |
| Journal | Naunyn-Schmiedeberg's Archives of Pharmacology |
| Volume | 346 |
| Issue number | 5 |
| State | Published - 1992 |
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Keywords
- α-adrenoceptor
- ATP
- bicarbonate-dependent transporter
- cardiomyocyte
- intracellular pH
ASJC Scopus subject areas
- Pharmacology
Cite this
Phenylephrine and ATP enhance an amiloride insensitive bicarbonate-dependent alkalinizing mechanism in rat single cardiomyocytes. / Terzic, Andre; Puceat, M.; Clement-Chomienne, O.; Vassort, G.
In: Naunyn-Schmiedeberg's Archives of Pharmacology, Vol. 346, No. 5, 1992, p. 597-600.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Phenylephrine and ATP enhance an amiloride insensitive bicarbonate-dependent alkalinizing mechanism in rat single cardiomyocytes
AU - Terzic, Andre
AU - Puceat, M.
AU - Clement-Chomienne, O.
AU - Vassort, G.
PY - 1992
Y1 - 1992
N2 - To expel the excess protons generated during a cellular acidification and to fully recover basal intracellular pH (pH(i)), cardiac cells rely on the amiloride-sensitive Na/H antiport. We report that rat single ventricular cardiomyocytes, loaded with the fluorescent pH indicator Snarf-1 and treated with inhibitors of the Na/H antiport, amiloride or its analogues, partially restored their pH(i) through a bicarbonate-dependent mechanism following an acidosis (imposed by the ammonia-pulse technique). In the presence of ethylisopropylamiloride (10 μM) or amiloride (1 mM) and 25 mM bicarbonate in the extracellular solution, the average time that cells needed to recover half of their pH(i), following the removal of 20 mM NH4Cl, was 3.4 min, while the rate of proton efflux was calculated to be 2.0 mM/min. The stilbene derivative, 4-4'-di-isothiocyanostilbene-2,2'-disulphonate (DIDS 200 μM), a known blocker of anion transporters, inhibited this recovery. Both phenylephrine (100 μM, 3 μM propranolol present), an α1-adrenoceptor agonist, and ATP (10 μM), a purinergic agonist, significantly enhanced the rate of proton efflux that was due to this HCO3-dependent alkalinizing mechanism. Phenylephrine and ATP also shortened by three-fold the time that a myocyte needed to recover half of its initial pH(i). This bicarbonate-dependent alkalinizing mechanism could provide an additional means by which cardiac cells recover their pH(i) from acidosis, especially under conditions in which the Na/H antiport is inhibited. Furthermore, catecholamines and ATP, which are released under various pathophysiological conditions often associated with intracellular acidosis, could play an important role in the modulation of pH(i) under these conditions.
AB - To expel the excess protons generated during a cellular acidification and to fully recover basal intracellular pH (pH(i)), cardiac cells rely on the amiloride-sensitive Na/H antiport. We report that rat single ventricular cardiomyocytes, loaded with the fluorescent pH indicator Snarf-1 and treated with inhibitors of the Na/H antiport, amiloride or its analogues, partially restored their pH(i) through a bicarbonate-dependent mechanism following an acidosis (imposed by the ammonia-pulse technique). In the presence of ethylisopropylamiloride (10 μM) or amiloride (1 mM) and 25 mM bicarbonate in the extracellular solution, the average time that cells needed to recover half of their pH(i), following the removal of 20 mM NH4Cl, was 3.4 min, while the rate of proton efflux was calculated to be 2.0 mM/min. The stilbene derivative, 4-4'-di-isothiocyanostilbene-2,2'-disulphonate (DIDS 200 μM), a known blocker of anion transporters, inhibited this recovery. Both phenylephrine (100 μM, 3 μM propranolol present), an α1-adrenoceptor agonist, and ATP (10 μM), a purinergic agonist, significantly enhanced the rate of proton efflux that was due to this HCO3-dependent alkalinizing mechanism. Phenylephrine and ATP also shortened by three-fold the time that a myocyte needed to recover half of its initial pH(i). This bicarbonate-dependent alkalinizing mechanism could provide an additional means by which cardiac cells recover their pH(i) from acidosis, especially under conditions in which the Na/H antiport is inhibited. Furthermore, catecholamines and ATP, which are released under various pathophysiological conditions often associated with intracellular acidosis, could play an important role in the modulation of pH(i) under these conditions.
KW - α-adrenoceptor
KW - ATP
KW - bicarbonate-dependent transporter
KW - cardiomyocyte
KW - intracellular pH
UR - http://www.scopus.com/inward/record.url?scp=0026490840&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026490840&partnerID=8YFLogxK
M3 - Article
C2 - 1335129
AN - SCOPUS:0026490840
VL - 346
SP - 597
EP - 600
JO - Naunyn-Schmiedeberg's Archives of Pharmacology
JF - Naunyn-Schmiedeberg's Archives of Pharmacology
SN - 0028-1298
IS - 5
ER -