Acidosis depresses delayed afterdepolarization in guinea pig myocardium

Abstract

We examined the relationship among intracellular sodium activity (aiNa), intracellular pH (pHi), and delayed afterdepolarization (DAD) in guinea pig ventricular papillary muscle fibers exposed to K-free solution in vitro, using Na+- and H+-selective microelectrodes. In unstimulated papillary muscles, exposure to K-free solution caused a rapid increase in aiNa of 16.2-22 mM at the end of a 20-min superfusion period with rates of 0.51-0.73 mM/min. This was paralleled by a decrease in intracellular pH of 0.10-0.15 units. DADs were induced after a train of driven action potentials 5-15 min after superfusion with K-free solution at the elevated aiNa from the steady-state level. Prevention of intracellular acidosis associated with the increased aiNa in K-free solution by external alkalosis at pH 8.0 enhanced the amplitude of the DAD, whereas restoration of external pH to 7.4 and a further acidification of external pH to 6.4 suppressed DADs. We concluded that intracellular acidosis associated with the increased aiNa per se increased the likelihood for inhibition of sarcoplasmic reticulum Ca2+ release in spite of increased cytosolic Ca2+.

Constitutive Intracellular Na + Excess in Purkinje Cells Promotes Arrhythmogenesis at Lower Levels of Stress Than Ventricular Myocytes From Mice With Catecholaminergic Polymorphic Ventricular Tachycardia

“…This is important because earlier studies have shown an important and complex relationship between changes in pH, [Na + ] i , and rate of stimulation, 43 which may have implications for the generation of DADs. 44 Finally, unlike in other experimental models such as dogs, 45 mouse Purkinje fibers exhibit a similar density of the inward rectifier K + current ( I K1 ) in PCs and VMs, as shown in our earlier study. 19 Thus, I K1 does not play a role in the preferential formation of DADs in PCs compared with VMs, at least in mice, but this cannot be ruled out for other species, including humans.…”

Effects of Stilbene Derivatives SITS and DIDS on Development of Intracellular Acidosis during Ischemia in Isolated Guinea Pig Ventricular Papillary Muscle In Vitro

“…The double barreled ion-selective microelectrodes were constructed and calibrated as described previously (8,34,35), using liquid-sensor cocktails (hydrogen ionophore Icocktail B, model 95293; Fluka Chemika-Biochemika, Buchs, Switzerland) for H+. Two capillaries were designated as tube A for a reference electrode measuring transmembrane potential and tube B for the ionic sensor.…”