DIFFERENTIAL INFLUENCE OF EXTRACELLULAR AND INTRACELLULAR PH ON K+ ACCUMULATION IN ISCHEMIC MAMMALIAN CARDIAC TISSUE

The separate and the combined influence of lowering extracellular and intracellular pH on the extracellular accumulation of K+ ions in ischa emic mammalian cardiac tissue was investigated. Isolated guinea-pig pa pillary muscles were superfused in vitro while micro-electrode measure ments of the transmembrane potentials and of the extracellular pH and K+ activity and of the intracellular pH and Na+ activity were performe d. Muscles were reversibly subjected to spaced episodes of simulated i schaemia, and ischaemic K+ accumulation was measured. During normal su perfusion, acidification of the intracellular pH (pH(i) similar to 6.8 ) effected by transient exposure to NH4+ containing superfusate was as sociated with an amiloride-sensitive rise of the intracellular Na+ act ivity (a(Na)(l)) from 5.1+/-0.5 to 19.5+/-2.4 mM. This increase was as sociated 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 be fore imposing ischaemia, extracellular K+ accumulation was increased c ompared to ischaemia alone. Surface K+ activity (a(K)(s)) measured aft er 10 min of ischaemia was 9.6+/-0.8 mM following intracellular acidif ication nu 6.4+/-0.4 mM following control superfusion. When the extrac ellular pH (pH(o)) was decreased to 6.85 prior to the ischaemic insult , extracellular K+ accumulation was not different from that observed d uring ischaemia after control superfusion (5.1+/-0.5 v 4.7+/-0.3 mM, r espectively, after 10 min of ischaemia). When combined intracellular a nd extracellular acidosis was produced before ischaemia, the enhancing influence of lowered pH, on K+ accumulation was not observed. In thes e acid loading conditions, a(Na)(l) rose to the same level as observed following NHC4+ withdrawal without simultaneous external acidificatio n (26.9+/-2.0 mM nu 23.9+/-2.0 mM, respectively). The results indicate that decreasing pH(i) before ischaemia accelerates the ischaemic incr ease of extracellular K+. On the other hand, although prior extracellu lar acidification by itself does not directly influence ischaemic K+ a ccumulation, it is in some way protective by reducing the intracellula r proton-stimulated K+ efflux. This reduction seems not to be due to d ecreased cellular Na+ loading. (C) 1995 Academic Press Limited