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First published online February 15, 2006
Journal of Experimental Biology 209, 916-926 (2006)
Published by The Company of Biologists 2006
doi: 10.1242/jeb.02087

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

Margarita A. Salas, Martín G. Vila-Petroff, Roque A. Venosa and Alicia Mattiazzi^*

Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, 60 y 120, 1900 La Plata, Argentina

^* Author for correspondence (e-mail: ramattia{at}atlas.med.unlp.edu.ar)

Accepted 10 January 2006

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 (pH_i) 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 pH_i 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 (0.5 µmol 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 pH_i 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.

Key words: toad, Buffo arenarum, ventricle, acidosis, muscle contraction

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