Effects of amiloride on pH regulation in canine cardiac Purkinje fibers.
Myocardial cells utilize membrane transport systems for proton extrusion as well as internal buffers to preserve pH homeostasis. Our laboratory had shown previously that amiloride (0.01-1.0 mM) causes a time- and dose-dependent increase in action potential duration, early after depolarizations and enhanced automaticity. Ion-selective microelectrode technique was used to evaluate whether the observed electrophysiologic effects of amiloride are linked to inhibition of Na/H exchange and subsequent inability of the myocardial cell to maintain steady-state intracellular pH (pHi), either under normal physiological conditions or in the presence of an imposed acid load. We analyzed different components of intracellular pH transients that occur in response to NH4Cl exposure and washout, which allowed us to quantitatively describe the effects of Na/H exchange inhibition in a multicellular preparation. Amiloride (0.01-1.0 mM) did not change the steady-state pHi, but did cause a dose-dependent increase in both the time for the pHi to reach a minimum value (time-to-peak) during washout of NH4Cl as well as in the absolute minimum value of pHi (peak acid). The effects of amiloride on pHi transients are rapidly reversible and antagonized by physiologic values of extracellular sodium activity. We conclude that Na/H exchange inhibition by amiloride does not cause intracellular acidosis under normal physiologic conditions, despite the dramatic changes in action potential characteristics. However, amiloride affected the time-to-peak and the peak acid value of the pHi transient during NH4Cl washout at concentrations that had no discernible effect on the overall time course of pHi recovery.
Brown
K K
KK
Department of Medicine, Duke University Medical Center, Durham, North Carolina.
Yee
R
R
Grant
A O
AO
Strauss
H C
HC
D000136:Acid-Base Equilibrium / Q000187:drug effects*; D000584:Amiloride / Q000494:pharmacology*; D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D006329:Heart Conduction System / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D011690:Purkinje Fibers / Q000187:drug effects / Q000378:metabolism*; D012756:Sheep; D012964:Sodium / Q000378:metabolism
D000643:Ammonium Chloride; D000584:Amiloride; D012964:Sodium