Na⁺/H⁺ Exchange In Cardiac Cells: Implications For Electrical And Mechanical Events During Intracellular pH Changes

Abstract

Intracellular acidification induced by changing from Hepes to a CO₂/HCO⁻ ₃ buffer results in an increase in the intracellular Na⁺ activity (aⁱ _Na). The exchanger is nearly inactive at intracellular pH (pH_i) of 7.2 − 7.0 and is strongly activated at pH_i below 7.0. The rate of rise in aⁱ _Na in conditions of a blocked Na⁺/K⁺ pump increases by a factor of 3.8 ± 0.9 (n=6) when pH_i drops from 7.2 ± 0.1 in Hepes to 6.8 ± 0.1 in 15% CO₂. Acid-induced increase in aⁱ _Na and accelerated rate of rise of aⁱ _Na can be blocked by amiloride (2.10⁻³ M) or by decreasing pH_O to 6.7. The rise in aⁱ _Na is associated with the generation of a Na⁺/K⁺ pump-dependent outward current. At low pH_O the increase in outward current is much smaller which demonstrates the absence of secondary pump stimulation when Na⁺/H⁺ exchange is inhibited. The Na⁺/K⁺ pump dependent hyperpolarization modifies spontaneous activity. Recovery of contractile force in an acid-loaded cell is related to the gain in aⁱ _Na.