Painted turtle cortex is resistant to an in vitro mimic of the ischemic mammalian penumbra.
Anoxia or ischemia causes hyperexcitability and cell death in mammalian neurons. Conversely, in painted turtle brain anoxia increases γ-amino butyric acid (GABA)ergic suppression of spontaneous electrical activity, and cell death is prevented. To examine ischemia tolerance in turtle neurons, we treated cortical sheets with an in vitro mimic of the penumbral region of stroke-afflicted mammalian brain (ischemic solution, IS). We found that during IS perfusion, neuronal membrane potential (V(m)) and the GABA(A) receptor reversal potential depolarized to a similar steady state (-92 ± 2 to -28 ± 3 mV, and -75 ± 1 to -35 ± 3 mV, respectively), and whole-cell conductance (G(w)) increased >3-fold (from 4 ± 0.2 to 15 ± 1 nS). These neurons were electrically quiet and changes reversed after reperfusion. GABA receptor antagonism prevented the IS-mediated increase in G(w) and neurons exhibited enhanced electrical excitability and rapid and irreversible rundown of V(m) during reperfusion. These results suggest that inhibitory GABAergic mechanisms also suppress electrical activity in ischemic cortex. Indeed, after 4 hours of IS treatment neurons did not exhibit any apparent damage; while at 24 hours, only early indicators of apoptosis were present. We conclude that anoxia-tolerant turtle neurons are tolerant of exposure to a mammalian ischemic penumbral mimic solution.
Division of Respiratory Medicine, Department of Pediatrics, University of California San Diego, La Jolla, California 92093-0735, USA. mpamenter@ucsd.edu
Matthew Edward
ME
Pamenter
David William
DW
Hogg
Xiang Qun
XQ
Gu
Leslie Thomas
LT
Buck
Gabriel George
GG
Haddad
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002545:Brain Ischemia / Q000473:pathology*; D002470:Cell Survival / Q000502:physiology; D002540:Cerebral Cortex / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000502:physiology; D004195:Disease Models, Animal; D002534:Hypoxia, Brain / Q000473:pathology / Q000503:physiopathology; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000473:pathology; D018377:Neurotransmitter Agents / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000502:physiology; D017966:Pyramidal Cells / Q000473:pathology; D012996:Solutions; D020521:Stroke / Q000473:pathology*; D014426:Turtles / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D018377:Neurotransmitter Agents; D012996:Solutions; D005680:gamma-Aminobutyric Acid; D011188:Potassium