THE IMPORTANCE OF SODIUM FOR ANOXIC TRANSMISSION DAMAGE IN RAT HIPPOCAMPAL SLICES - MECHANISMS OF PROTECTION BY LIDOCAINE

1. The effect of sodium influx on anoxic damage was investigated in ra t hippocampal slices. Previous experiments demonstrated that a concent ration of tetrodotoxin which blocks neuronal transmission protects aga inst anoxic damage. In this study we examined low concentrations of li docaine (lignocaine; which do not block neuronal transmission), for th eir effect on recovery of the evoked population spike recorded from th e CA1 pyramidal cell layer. 2. Recovery of the population spike, measu red 60 min after a 5 min anoxic period, was 4 +/- 2% of its preanoxic, predrug level. Lidocaine concentrations of 10, 50, and 100 mu M signi ficantly improved recovery to 56 +/- 12, 80 +/- 7 and 70 +/- 14%, resp ectively. 3. Lidocaine (10 mu M) did not alter the size of the evoked response before anoxia and had no significant effect on potassium leve ls or calcium influx during anoxia. It did, however, reduce cellular s odium levels (146 +/- 7 vs. 202 +/- 12 nmol mg(-1)) and preserve ATP l evels (2.17 +/- 0.07 vs. 1.78 +/- 0.07 nmol mg(-1)) during anoxia. All values were measured at the end of 5 min of anoxia except those for C a2+ influx which were measured during 10 min of anoxia. 4. High concen trations of lidocaine (100 mu M) did not improve recovery significantl y over that observed with 10 mu M. They also had no significantly grea ter effects on sodium levels than 10 mu M lidocaine (137 +/- 12 vs. 14 6 +/- 7 nmol mg(-1)); however, 100 mu M lidocaine significantly improv ed potassium (202 +/- 18 vs. 145 +/- 6 nmol mg(-1)) and ATP (2.57 +/- 0.06 vs. 2.17 +/- 0.07 nmol mg(-1)) levels, while reducing calcium inf lux (7.76 +/- 0.12 vs. 9.24 +/- 0.39 nmol mg(-1) (10 min)(-1)) when co mpared with 10 mu M lidocaine. 5. We conclude that sodium influx and A TP depletion are of major importance in anoxic damage since 10 mu M li docaine reduced these changes during anoxia and improved recovery of t he population spike. In addition, our results indicate that the proper ties of the sodium channel are altered during anoxia, since sodium inf lux is blocked by a concentration of lidocaine that does not affect th e population spike in the preanoxic period.