Coupling of cellular energy state and ion homeostasis during recovery following brain ischemia

The present experiments were undertaken to explore the relationship between recovery of cerebral energy state following transient ischemia, and resumption of Na+/K+ transport, as this is reflected in changes in extracellular K+ concentration ([K+]c). Cerebral energy state was evaluated by measurements of cerebral cortical concentrations of phosphocreatine (PCr), ATP, ADP, and AMP at the end of 15 min of severe, incomplete ischemia, as well as after 2 and 5 min of recirculation. Derivation of intracellular pH (pHi) allowed calculation of 'free' ADP (ADPf) and AMP (AMPf) concentrations. Changes in [K+]e were measured by an ion-sensitive microelectrode. The results showed that tissue ATP concentration, which was close to zero after 15 min of ischemia, rose to 30% of control after 2 min, and to 60% of control after 5 min of recirculation. However, since the adenine nucleotide pool was reduced by the ischemia the latter value represents extensive or complete phosphorylation of that pool, as reflected in a normalized ATP/ADPf ratio. During recirculation, the concentration of pyruvate rose, but the lactate content remained unchanged, suggesting that the substrate for oxidative metabolism was exogenous glucose. Resumption of Na+/K+ transport, as reflected in the [K+]e began after 2-3 min, and a normal [K+]e was attained within 5 min. The results demonstrate that transport of Na+ and K+ is resumed at tissue ATP concentrations which are only 30-40% of control. It is discussed whether this reflects relatively extensive rephosphorylation of the remaining adenine nucleotide pool, or if compartmentation of adenine nucleotides exists during recirculation.