Analysis of Cl- -HCO3(-) exchange during recovery from intracellular acidosis in cardiac Purkinje strands

Vanheel, Bert; Hemptinne, Alexandre de; Leusen, I

doi:10.1152/ajpcell.1984.246.5.c391

Cited by 52 publications

(31 citation statements)

References 25 publications

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“…Physiological importance of the Na+-HCO3-symport It is puzzling that, despite the clear evidence presented here, HCO3--activated acid-equivalent extrusion has not hitherto been observed in mammalian cardiac muscle (Vaughan-Jones, 1982;Vanheel et al 1984;Weissberg et al 1989). The reason for this is not known.…”

mentioning

confidence: 58%

“…Deitmer & Ellis, 1980;Kaila & Vaughan-Jones, 1987). Nevertheless, some studies looked specifically for the existence of HC03--dependent acid extrusion in cardiac tissue and failed to detect it (Vaughan-Jones, 1982;Vanheel, de Hemptinne & Leusen, 1984;Piwnica-Worms, Jacob, Horres & Lieberman, 1985;Weissberg et al 1989). More recently, Liu et al (1990) have described a sodium-and bicarbonate-dependent acid extrusion mechanism in the chick heart but they attributed this to a Na+-dependent Cl--HCO3-exchanger.…”

Section: Discussionmentioning

confidence: 99%

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Na(+)‐HCO3‐ symport in the sheep cardiac Purkinje fibre.

Dart¹,

Vaughan‐Jones²

1992

The Journal of Physiology

135

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SUMMARY1. Intracellular pH (pHi) was recorded in isolated sheep cardiac Purkinje fibres using liquid sensor ion-selective microelectrodes in conjunction with conventional (3 M-KCl) microelectrodes (to record membrane potential).2. In HEPES-buffered solution (pHo 7 4), pHi recovery from an intracellular acid load (20 mM-NH4Cl removal) was blocked by 1 mM-amiloride, consistent with the inhibition of Na+-H+ exchange. Replacement of the HEPES buffer with C02-HC03-caused a transient acidosis followed by an amiloride-resistant recovery of pHi to more alkaline levels (n = 43). This implies the presence of a HC03--dependent pHi regulatory mechanism.3. Comparison of the membrane potential with the equilibrium potential for HC03-ions (EHCO3) estimated during amiloride-resistant pHi recovery, showed that for polarized fibres (membrane potential Em -80 mV), there was a net outward electrochemical driving force for HC03-ions. Hence the amiloride-resistant pHi recovery cannot be explained in terms of passive HC03-influx through membrane channels.4. Removal of external Na+ (Na+ replaced by N-methyl-D-glucamine) inhibited HC03--dependent pHi recovery, whereas removal of external Cl-(leading to depletion of internal Cl-; Cl-replaced by glucuronate) or short-term removal of extracellular K+ had no inhibitory effect. We suggest that a Na+-HCO3-co-influx causes the recovery. Replacement of external Na+ with Li+ greatly reduced HC03--dependent pHi recovery indicating that Li+ cannot readily substitute for Na+ on the co-transport.5. The stilbene drug DIDS (4,4-diisothiocyano-stilbene-disulphonic acid, 500 ftM) slowed HC03--dependent pHi recovery.6. Depolarization of the membrane potential in high K+ (44 5 mM) solution or with 5 mm-BaCl2 had no effect upon the rate of HC03--sensitive pHi recovery. This observation, when coupled with the fact that activation of HC03--dependent pH1 recovery was associated with no consistent change of membrane potential, suggests that the Na+-HCO3-co-influx is electroneutral and voltage insensitive.7. HC03--dependent pHi recovery was unaffected by the Na+-K+-2Cl-cotransport inhibitor, bumetanide (150 /LM).8. The contribution of Na+-H+ exchange and Na+-HCO3-co-transport to net acid efflux was assessed. At a pHi of 6-6, we estimate that the co-transport should account for 20% of total acid equivalent efflux. Because of the different slopes for the pHi MS 9393 C. DART AND R. D. VAUGHAN-JONES dependence of the two transporters, this contribution should increase as pHi increases so that, at a pHi of 7 0, Na'-HCO3-symport should account for approximately 30% of total acid-equivalent efflux.9. It is concluded that in C02-HCO3--buffered media, acid equivalent extrusion is mediated not only by Na+-H+ exchange but also by an electroneutral Na'-HCO3-co-influx mechanism.

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mentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Na(+)‐HCO3‐ symport in the sheep cardiac Purkinje fibre.

Dart¹,

Vaughan‐Jones²

1992

The Journal of Physiology

135

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“…Vanheel, de Hemptinne & Leusen, 1984). This may explain the observation that GABA had a slight depolarizing action in the nominal absence of HCO3-, an effect which was potentiated in the absence of extra-and intracellular Cl-.…”

Section: Gaba-gated Bicarbonate Conductancementioning

confidence: 95%

Influence of GABA‐gated bicarbonate conductance on potential, current and intracellular chloride in crayfish muscle fibres.

Kaila¹,

Pasternack²,

Saarikoski³

et al. 1989

The Journal of Physiology

115

109

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SUMMARY1. The effects of y-aminobutyric acid (GABA) on membrane potential and conductance as well as on the intracellular Cl-activity (ai4k) and intracellular pH (pHi) were studied in crayfish muscle fibres using a three-microelectrode voltage clamp and ion-selective microelectrodes. In the presence of C02-HC03-, the intracellular HCO3-activity (a' o3) was estimated from pHi.2. In a nominally HCO3 -free solution, a near-saturating concentration of GABA (0-2 mM) produced a marked increase in membrane conductance but little change in potential. In a solution containing 30 mM-HCO3-(equilibrated with 5 % CO2 + 95 % air; pH 7-4), the GABA-induced increase in conductance was associated with a depolarization of about 15 mV, with an increase in ai1 and with a decrease in ah-o.All these effects were blocked by picrotoxin (PTX). The depolarizing action of GABA was augmented following depletion of extracellular and intracellular Cl-.3. The GABA-induced increase in a', which took place in the presence of HCO3 was blocked by clamping the membrane potential at its resting level. This indicates that the increase in a'1 was due to passive redistribution of Cl-. In both the presence and absence of HC03-, the GABA-activated transmembrane flux of Cl-showed reversal at the level of the resting potential, which indicates that under steady-state conditions the Cl-equilibrium potential (Ec1) is identical to the resting potential.4. In a Cl--free, 30 mM-HCO3--containing solution, 0-5 mM-GABA produced a PTX-sensitive increase in conductance which amounted to 15 % of the conductance activated in the presence of Cl-. In the absence of both Cl-and HC03-, the respective figure was 2-8 %. Assuming constant-field conditions, the conductance data yielded a permeability ratio PHCo3/PC1 of 0-42 for the GABA-activated channels.5. In a Cl--containing, HC03--free solution, the reversal potential of the GABAactivated current (EGABA) was, by about 1 mV, less negative than the resting membrane potential (RP). In a solution containing Cl-and 30 mM-HCO3-, EGABA -RP was 12 mV. Simultaneous measurements of EGABA, aci and allCO3 (pHi) gave a PHCO3/PC1 value of 0 33.6. In a Cl--free, HC03--containing solution EGABA was close to the HC03-* To whom correspondence should be addressed. 6 PHY 416K. KAILA AND OTHERS equilibrium potential (EHCO3) and an experimental acidosis which produced a negative shift in EHCO3 was associated with a similar shift in EGABA.7. The present results show that HCO3-permeability of GABA-gated channels can lead to a significant deviation of EGABA from Ecl, and, in particular, to a depolarizing effect of GABA in the absence of a postsynaptic, inwardly directed Clpump. The dependence of EGABA on HCO3-permeability may provide a novel link between postsynaptic regulation of pHi and the efficacy of synaptic inhibition.

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“…Therefore, interpretations of the present results entirely rest on the assumption that SITS and DIDS at the concentrations employed in the present experiments mainly act as a blocker for Cl--HCO3-exchange; If this is the case, then the present findings of SITS and DIDS-induced attenuation of the development of intracellular acidosis during the initial phase of simulated ischemia could be explained as a consequence of the blockade of the CI--HCO3-exchange. This idea might appear surprising at first because it has been believed that the hypoxic acidification is primarily due to the production of lactic acid (2,4,51), and Cl--HCO3-exchange plays a role in the recovery from intracellular alkalinization, while the exchanger activity is decreased at acid pHi (15,18,21,23). Moreover, in cultured chick heart cells, a Nat-dependent Cl--HCO3-exchange regulates pHi after cell acidification and can cause cell alkalinization (17).…”

Section: Actions Of Sits and Dids On Action Potentials During Ischemiamentioning

confidence: 99%

“…Most studies suggest that the recovery of pH; from acidosis is mediated by several sarcolemmal ion transports including Na+-H+ exchange, Na+-HCO3-cotransport, and Na+-dependent Cl--HCO3-exchange, but the recovery from alkalosis is mediated by Na+-independent Cl--HCO3-exchange. In Purkinje fiber, Vanheel et al (21) showed that acid extrusion was not impaired when the [Cl-];-[HCO3-]o exchange was blocked, whereas other investigators suggested that the Na+-dependent CI--HCO3-exchange plays a significant role in pH, regulation in isolated chick heart cells (17) and in quiescent Purkinje fibers (22,23). More recently, the existence of HC03-dependent pH, regulation (Na+-HCO3 symport) in the guinea pig ventricular myocyte has been also proposed (24).…”

mentioning

confidence: 99%

Effects of Stilbene Derivatives SITS and DIDS on Development of Intracellular Acidosis during Ischemia in Isolated Guinea Pig Ventricular Papillary Muscle In Vitro

Lai

Liu

Nishi

1996

Japanese Journal of Pharmacology

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ABSTRACT-Using ion-selective microelectrode techniques, we investigated the effects of 4-acetamido-4'-isothiocyanatostilbene-2,2 disulfonic acid (SITS) and 4,4' -diisothiocyanostilbene-2,2 disulfonic acid (DIDS), which are known as Cl--HCO3-exchange blockers, on action potentials and intracellular pH (pH;) in guinea pig ventricular papillary muscles subjected to simulated ischemia. Simulated ischemia was produced by stopping the flow of superfusing solution and then covering the preparations with mineral oil. Simulated ischemia induced a progressive decrease in the maximum upstroke rate and resting membrane potentials, shortened action potential duration, and resulted in cessation of action potentials within 10-12 min after the onset of simulated ischemia. The pH;-measurements revealed progressive intracellular acidosis during the period of simulated ischemia. SITS (0.5 mM) or DIDS (0.1 mM) delayed the onset of ischemiainduced deterioration of action potentials and prolonged the time to cessation of action potentials. SITS or DIDS (0.1-0.5 mM) induced an increase in pH, in HCO3--buffered solution and suppressed the development of intracellular acidosis during ischemia. Under the external Cl--free condition, the time to cessation of action potentials caused by ischemia was significantly delayed, and the development of intracellular acidosis during ischemia was attenuated. The present results indicate that activation of the Cl--HC03-exchange system would be involved, in part, in the development of intracellular acidosis during cardiac ischemia.

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Analysis of Cl- -HCO3(-) exchange during recovery from intracellular acidosis in cardiac Purkinje strands

Cited by 52 publications

References 25 publications

Na(+)‐HCO3‐ symport in the sheep cardiac Purkinje fibre.

Na(+)‐HCO3‐ symport in the sheep cardiac Purkinje fibre.

Influence of GABA‐gated bicarbonate conductance on potential, current and intracellular chloride in crayfish muscle fibres.

Effects of Stilbene Derivatives SITS and DIDS on Development of Intracellular Acidosis during Ischemia in Isolated Guinea Pig Ventricular Papillary Muscle In Vitro

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