Differential influence of extracellular and intracellular pH on K+ accumulation in ischaemic mammalian cardiac tissue.

The separate and the combined influence of lowering extracellular and intracellular pH on the extracellular accumulation of K+ ions in ischaemic mammalian cardiac tissue was investigated. Isolated guinea-pig papillary muscles were superfused in vitro while micro-electrode measurements of the transmembrane potentials and of the extracellular pH and K+ activity and of the intracellular pH and Na+ activity were performed. Muscles were reversibly subjected to spaced episodes of simulated ischaemia, and ischaemic K+ accumulation was measured. During normal superfusion, acidification of the intracellular pH (pHi approximately 6.8) effected by transient exposure to NH+4 containing superfusate was associated with an amiloride-sensitive rise of the intracellular Na+ activity (aiNa) from 5.1 +/- 0.5 to 19.5 +/- 2.4 mM. This increase was associated with a transient hyperpolarization of the membrane potential and shortening of the action potential duration from 190 +/- 7 to 111 +/- 16 ms. When a similar intracellular acidosis was induced 3 to 5 min before imposing ischaemia, extracellular K+ accumulation was increased compared to ischaemia alone. Surface K+ activity (asK) measured after 10 min of ischaemia was 9.6 +/- 0.8 mM following intracellular acidification v 6.4 +/- 0.4 mM following control superfusion. When the extracellular pH (pHo) was decreased to 6.85 prior to the ischaemic insult, extracellular K+ accumulation was not different from that observed during ischaemia after control superfusion (5.1 +/- 0.5 v 4.7 +/- 0.3 mM, respectively, after 10 min of ischaemia). When combined intracellular and extracellular acidosis was produced before ischaemia, the enhancing influence of lowered pHi on K+ accumulation was not observed. In these acid loading conditions, aiNa rose to the same level as observed following NH+4 withdrawal without simultaneous external acidification (26.9 +/- 2.0 mM v 23.9 +/- 2.0 mM, respectively). The results indicate that decreasing pHi before ischaemia accelerates the ischaemic increase of extracellular K+. On the other hand, although prior extracellular acidification by itself does not directly influence ischaemic K+ accumulation, it is in some way protective by reducing the intracellular proton-stimulated K+ efflux. This reduction seems not to be due to decreased cellular Na+ loading.