NA-INDUCED RELEASE OF NOREPINEPHRINE FROM SPINAL-CORD SLICES( CHANNELBLOCK PREVENTS THE ISCHEMIA)

The principal finding of the present study with rat spinal cord slices was the novel demonstration of the [Ca2+](o)-independent effect of is chemia on norepinephrine release and its antagonism by tetrodotoxin an d low temperature (10 degrees C). Our finding that tetrodotoxin antago nized the effects of glucose deprivation on norepinephrine release in a [Ca2+](o)-independent way suggests that Na+ channel block alone, i.e ., the prevention of Na+ accumulation, may account for the protective action. Low temperature completely prevented the effect of ischemia on norepinephrine release but did not change the release associated with axonal activity. This finding is in good agreement with the observati on that small changes in bl ain temperature critically determine the e xtent of neuronal injury from ischemia and suggests that both [Ca2+](o )-independent release and cell injury are associated with the norepine phrine membrane carrier. It is suggested, therefore, that drugs able t o attenuate the increase in [Na+](i) during ischemia may be useful age nts to protect against ischemic damage if given before the insult. (C) 1998 Elsevier Science B.V.