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

SALAS MA; VILA-PETROFF MG; VENOSA RA; MATTIAZZI A

JOURNAL OF EXPERIMENTAL BIOLOGY

The Company of Biologists

Año: 2006 vol. 209 p. 916 - 926

0022-0949

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 mechanism of this recovery are far from being understood, specially in those species in which excitation contraction coupling, differs from that of 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 acidosis. This contractile pattern was associated with an initial decrease in pHi that recovered to control values in spite of the persistent extracellular acidosis. Blockade of the Na+/H+ exchanger (NHE) with cariporide (5µM), produced a complete inhibition of the pHi restitution, without affecting 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 NCX by KB-R, 1µM for myocytes and 20µM for ventricular strips, or of L-type Ca2+ channels by nifedipine, 0.5µM, completely abolished the mechanical recovery. Acidosis also produced an increase in action potential duration that remained prolonged all along 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 the recovery of pHi 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, are involved in the increase of the Ca2+  transient that mediates contractile recovery from acidosis.