Acceleration of H+ Extrusion via Na+-H+ Exchange in Guinea-Pig Ventricular Papillary Muscle under Intracellular Acidic Condition.

Abstract

We investigated mechanisms by which intracellular pH was regulated under intracellular acidic condition in resting guinea-pig ventricular papillary muscles in vitro. Intracellular sodium ion activity (aiNa), intracellular and surface pH (pHi and pHs) were measured with Na(+)- and H(+)-selective microelectrodes and resting tension was measured. By exposure to 0 mM K solution aiNa and resting tension increased progressively while pHi decreased but reached the steady level of pH 6.95. pHs which was lower than external bulk pH (pHo) decreased progressively by exposure to 0 mM K solution. In 4 mM K solution, amiloride (1 mM), an inhibitor of Na(+)-H+ exchange, induced a reversible decrease in both aiNa and pHi, and an increase in pHs. Changes in pHi and pHs induced by application of amiloride in 0 mM K solution were larger than those in 4 mM K solution. The rate of decrease in pHi induced by amiloride became larger at longer exposure to 0 mM K solution. Lowering pHo from 7.4 to 6.4 induced a larger decrease in pHi in 0 mM K solution than that in 4 mM K solution. Lowering pHo from 7.4 to 5.4 reversed the difference between pHs and pHo. These results suggest that in guinea-pig papillary muscle, Na(+)-H+ exchange is active to regulate intracellular H+ under resting condition and under intracellular acidic condition, H+ extrusion via the Na(+)-H+ exchange would be accelerated not only by the net thermodynamic driving force for Na+ and H+ but also by other factors.

Effect of Amiloride on Ischaemia and Reperfusion Injury in Isolated, Perfused Rat Hearts

“…Measurements of intracellular cation contents revealed that amiloride could inhibit cellular Na accumulation in the early stage of reperfusion and cellular Ca 2 accumulation in the late stage. It has been proposed that intracellular H accumulation due to ischaemia facil-itates Na /H exchange during reperfusion (7,9,12,15) and causes subsequent Ca 2 influx through Na /Ca 2 exchange (19,20). Hence, it seems likely that amiloride inhibited cellular Na accumulation through its blocking action on Na /H exchange in the early stage of reperfusion, and prevented consequent Ca 2 overload via Na /Ca 2 exchange in the late stage.…”

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.…”

“…The acidic intracellular environment would favor the exchange of extracellular Na+ for intracellular H+ via Na+-H+ exchange, resulting in an abnormal gain of intracellular Na+ (5)(6)(7)(8). An accumulation of Na+ inside the cell would lead to subsequent Ca2+ entry via Na+-Ca 2+ exchange.…”