THE INFLUENCE OF PH ON CELLULAR CALCIUM INFLUX DURING ISCHEMIA

The objective of this study was to explore how alterations in tissue p H during ischemia influence cell calcium uptake, as this is reflected in the extracellular calcium concentration (Ca(e)2+). Variations in pH were achieved by making animals hypo-, normo- or hyperglycemic prior to cardiac arrest ischemia or by increasing preischemic PCO2 in normog lycemic animals. For comparison, the N-methyl-D-aspartate (NMDA) recep tor antagonist dizocilpine maleate (MK-801) was given prior to inducti on of ischemia. In some experiments the effect of acidosis on K- efflu x and Na+ influx were studied as well. In hypoglycemic subjects, the r eduction of Ca(e)2+ during ischemia was very rapid, 90% of the reducti on occurring within 4.7 s. Normoglycemic animals showed a slower rate of reduction of Ca(e)2+. Hyperglycemic animals displayed an even slowe r rate of reduction and a biphasic response in which the initial, fast er influx of Ca2+ was followed by a conspicuously slow one. This secon d phase led to a very gradual decrease in Ca(e)2+ a stable level being reached first after 6-7 min. This marked delay in calcium influx duri ng ischemia was very similar in hypercapnic animals, who showed an ext racellular pH during ischemia as low as hyperglycemic subjects. The ef fect of acidosis was duplicated by MK-801, suggesting that low pH redu ces calcium influx by blocking NMDA-gated ion channels.