INFLUENCE OF PH ON CALCIUM INFLUX DURING HYPOXIA IN RAT CORTICAL BRAIN-SLICES

Background and Purpose Acidity of brain intracellular and extracellula r fluids appears to increase brain injury from stroke, but low extrace llular pH decreases the activity of N-methyl-D-aspartate receptor ion channels and decreases calcium influx into isolated neurons. To furthe r investigate the role of acid-base balance in hypoxic brain injury, w e studied the influences of intracellular and extracellular pH on calc ium influx in cortical brain slices during hypoxia. Methods Intracellu lar calcium ([Ca2+]i) and pH (pH(i)) were measured fluorometrically wi th the dyes fura-2 and biscarboxyethyl carboxyfluorescein, respectivel y, during two types of hypoxia: (1) slice perfusate equilibrated with N2/CO2 at pH 6.6 or 6.2 (''gaseous hypoxia'') or (2) perfusate equilib rated with 95% O2/5% CO2 plus 100 mumol/L NaCN at pH 7.3, 6.6, or 6.2 (''chemical hypoxia''). Results Changes in perfusate pH under aerobic conditions did not change [Ca2+]i. However, influx of calcium caused b y gaseous or chemical hypoxia increased significantly with decreasing perfusate pH. During chemical hypoxia, the elevation in [Ca2+]i at per fusate pH 6.2 was twice that at perfusate pH 7.3. Change in [Ca2+]i wa s correlated with perfusate pH but not pH(i). Conclusions These result s, which differ from previous studies showing acid inhibition of calci um influx in isolated neurons, suggest that low extracellular pH may e xacerbate cellular injury during severe hypoxia or ischemia in the int act brain.