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 superfusedin vitrowhile 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 (pHi6.8) effected by transient exposure to NH+4containing superfusate was associated with an amiloride-sensitive rise of the intracellular Na+activity (aiNa) from 5.1±0.5 to 19.5±2.4 m . 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 m following intracellular acidificationv6.4±0.4 m 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±0.5v4.7±0.3 m , respectively, after 10 min of ischaemia). When combined intracellular and extracellular acidosis was produced before ischaemia, the enhancing influence of lowered pHion K+accumulation was not observed. In these acid loading conditions, aiNarose to the same level as observed following NH+4withdrawal without simultaneous external acidification (26.9±2.0 m v23.9±2.0 m , respectively). The results indicate that decreasing pHibefore 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.