Anoxia-induced Increase Research Articles

Role of ATP-sensitive K+ channels during anoxia: major differences between rat (newborn and adult) and turtle neurons.

1. It is well known that anoxia induces an increase in extracellular K+. The underlying mechanisms for the increase, however, are not well understood. In the present study, we performed electrophysiological, pharmacological and receptor autoradiographic experiments in an attempt to examine K+ ionic homeostasis during anoxia. Ion-selective microelectrodes were employed to measure intracellular and extracellular K+ activity from hypoglossal neurons in brain slices. 2. During 3-4 min anoxia, adult hypoglossal neurons lose a large amount of their intracellular K+ and this contributes in a major way to the 8-fold increase in extracellular K+. 3. Loss of intracellular K+ from hypoglossal neurons is, to a great extent, due to activation of certain specific K+ channels. Glibenclamide, a potential sulphonylurea ligand and a specific blocker of ATP-sensitive K+ (KATP) channels, has no effect on K+ homeostasis during oxygenated states, but almost halves the anoxia-induced increase in extracellular K+ in the adult rat. 4. [3H]glibenclamide autoradiography shows that the hypoglossal nucleus in the adult rat has high sulphonylurea receptor density, a finding that is consistent with our electrophysiological observation. 5. Since we have previously shown that newborn mammals and reptiles are more resistant to O2 deprivation than adult mammals, we performed comparative studies among adult rat, newborn rat and adult turtle. In sharp contrast to the adult rat, extracellular K+ activity in newborn rat and adult turtle brain increases little (10 to 100 times less than the adult rat) and glibenclamide has a small and insignificant effect on K+ efflux in the newborn rat and none in the turtle. Glibenclamide receptor binding sites are much lower in the newborn rat than in the adult rat central nervous system (CNS) and barely detectable in the turtle brain. 6. These results support the hypothesis that in the adult rat, K+ is lost during anoxia from neurons through sulphonylurea receptor or KATP channels in a major way. Generally, however, KATP channels are poorly expressed in the newborn rat and adult turtle CNS and have little role to play during O2 deprivation.

Effect of anoxia on intracellular and extracellular potassium activity in hypoglossal neurons in vitro

1. A brain slice preparation was used to study the hypoglossal (XII) neuronal response to anoxia. Both intra- and extracellular potassium activities (K+i,K+o) were measured by the use of ion-selective microelectrodes, and K+ flux was assessed by the use of pharmacologic blockers. 2. Extracellular recordings showed that a short period of anoxia (4 min) induced an increase in K+o of 26.4 +/- 7.5 mM (mean +/- SD, n = 20) in the XII nucleus of adult rats. 3. Intracellular recordings (n = 31) in XII neurons showed a substantial decrease in K+i during anoxia. Fourteen neurons were analyzed in detail and these showed that XII neurons depolarized to -25.3 +/- 7.7 mV, whereas K+i dropped from 93.6 +/- 14.9 to 32 +/- 9.0 mM. These results strongly suggested that K+ is lost from XII neurons during anoxia. 4. Although the extracellular space (ECS) shrank by approximately 50% during anoxia, the possibility that the increase in K+o and decrease in K+i were mainly caused by shrinkage of the ECS and swelling of intraneuronal space was excluded to a great degree because the changes in K+i and K+o during anoxia were relatively very large. 5. To study the mechanisms by which K+ is lost from XII neurons, we used several pharmacologic blockers. High concentration of ouabain (10 mM) and strophanthidin (80 microM) increased K+o from baseline (3-4 mM) to 40.9 +/- 2.5 mM (n = 6) but did not abolish an additional anoxia-induced increase in K+o, suggesting that mechanisms other than Na(+)-K(+)-adenosine triphosphatase inhibition were also responsible for the anoxia-induced K+ leakage.(ABSTRACT TRUNCATED AT 250 WORDS)