Contractile recovery from acidosis in toad ventricle is independent of intracellular pH and relies upon Ca2+ influx

Abstract

SUMMARY Hypercapnic acidosis produces a negative inotropic effect on myocardial contractility followed by a partial recovery that occurs in spite of the persistent extracellular acidosis. The underlying mechanisms of this recovery are far from understood, especially in those species in which excitation–contraction coupling differs from that of the mammalian heart. The main goal of the present experiments was to obtain a better understanding of these mechanisms in the toad heart. Hypercapnic acidosis,induced by switching from a bicarbonate-buffered solution equilibrated with 5%CO2 to the same solution equilibrated with 12% CO2,evoked a decrease in contractility followed by a recovery that reached values higher than controls after 30 min of continued acidosis. This contractile pattern was associated with an initial decrease in intracellular pH(pHi) that recovered to control values in spite of the persistent extracellular acidosis. Blockade of the Na+/H+ exchanger(NHE) with cariporide (5 μmol l–1) produced a complete inhibition of pHi restitution, without affecting the mechanical recovery. Hypercapnic acidosis also produced a gradual increase of diastolic and peak Ca2+i transient values, which occurred immediately after the acidosis was settled and persisted during the mechanical recovery phase. Inhibition of Ca2+ influx through the reverse mode of the Na+/Ca2+ exchanger (NCX) by KB-R (1 μmol l–1 for myocytes and 20 μmol l–1 for ventricular strips), or of L-type Ca2+ channels by nifedipine (0.5μmol l–1), completely abolished the mechanical recovery. Acidosis also produced an increase in the action potential duration. This prolongation persisted throughout the acidosis period. Our results show that in toad ventricular myocardium, acidosis produces a decrease in contractility,due to a decrease in Ca2+ myofilament responsiveness, followed by a contractile recovery, which is independent of pHi recovery and relies on an increase in the influx of Ca2+. The results further indicate that both the reverse mode NCX and the L-type Ca2+channels, appear to be involved in the increase in intracellular Ca2+ concentration that mediates the contractile recovery from acidosis.

Hypercapnic Acidosis Reduces Contractile Function in the Ventricle of the Armored Catfish,Pterygoplichthys pardalis

“…However, this seems unlikely because myocardial force is known to recover during persistent acidosis with a fairly rapid time course (∼5 min) in both mammals (Orchard 1987) and amphibians (Salas et al 2006). Alternatively, the lack of force recovery during persistent acidosis may be because acid extrusion mechanisms were not activated (or sufficiently activated).…”

Multiple H+ sensors mediate the extracellular acidification-induced [Ca2+]i elevation in cultured rat ventricular cardiomyocytes

“…However, the concrete mechanisms of Ca 2+ transients are diverse and uncertain. Several studies have shown that the increase of [Ca 2+ ] i is induced by the influx of extracellular Ca 2+ via membrane Ca 2+ channels or Na + /Ca 2+ exchangers34. However, the increase of intracellular Ca 2+ also can be resulted from the mobilization of sarcoplasmic reticulum (SR) during acidosis56.…”

High [Na+]iin cardiomyocytes from rainbow trout

“…In many studies, an inhibitor of the Na ϩ -K ϩ -ATPase, such as strophanthidin or ouabain, is included in the calibration solution to facilitate the equilibration between extracellular and intracellular [Na ϩ ]. However, many cells died during calibration in the presence of 10 M ouabain as has been used for isolated toad cardiomyocytes (23). We are uncertain whether this was due to Ca 2ϩ overload.…”