Neuronal membrane potential is mildly depolarized in the anoxic turtle cortex.
Neuronal membrane potential (E(m)) regulates the activity of excitatory voltage-sensitive channels. Anoxic insults lead to a severe loss of E(m) and excitotoxic cell death (ECD) in mammalian neurons. Conversely, anoxia-tolerant freshwater turtle neurons depress energy usage during anoxia by altering ionic conductance to reduce neuronal excitability and ECD is avoided. This wholesale alteration of ion channel and pump activity likely has a significant effect on E(m). Using the whole-cell patch clamp technique we recorded changes in E(m) from turtle cortical neurons during a normoxic to anoxic transition in the presence of various ion channel/pump modulators. E(m) did not change with normoxic perfusion but underwent a reversible, mild depolarization of 8.1+/-0.2 mV following anoxic perfusion. This mild anoxic depolarization (MAD) was not prevented by the manipulation of any single ionic conductance, but was partially reduced by pre-treatment with antagonists of GABA(A) receptors (5.7+/-0.5 mV), cellular bicarbonate production (5.3+/-0.2 mV) or K(+) channels (6.0+/-0.2 mV), or by perfusion of reactive oxygen species scavengers (5.2+/-0.3 mV). Furthermore, all of these treatments induced depolarization in normoxic neurons. Together these data suggest that the MAD may be due to the summation of numerous altered ion conductance states during anoxia.
Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada.
Matthew Edward
ME
Pamenter
Leslie Thomas
LT
Buck
D000818:Animals; D001639:Bicarbonates / Q000737:chemistry; D016923:Cell Death; D000860:Hypoxia; D007473:Ion Channels / Q000737:chemistry; D007477:Ions; D008564:Membrane Potentials; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000737:chemistry; D017382:Reactive Oxygen Species; D011963:Receptors, GABA-A / Q000737:chemistry; D014426:Turtles
D001639:Bicarbonates; D007473:Ion Channels; D007477:Ions; D017382:Reactive Oxygen Species; D011963:Receptors, GABA-A; D011188:Potassium; D010100:Oxygen