Ionic mechanisms underlying differential vulnerability to ischemia in striatal neurons.
Brain cells express extremely different sensitivity to ischemic insults. The reason for this differential vulnerability is still largely unknown. Here we discuss the ionic bases underlying the physiological responses to in vitro ischemia in two neostriatal neuronal subtypes exhibiting respectively high sensitivity and high resistance to energy deprivation. Vulnerable neostriatal neurons respond to ischemia with a membrane depolarization. This membrane depolarization mainly depends on the increased permeability to Na+ ions. In contrast, resistant neostriatal neurons respond to ischemia with a membrane hyperpolarization due to the opening of K+ channels. Interestingly, in both neuronal subtypes the ischemia-dependent membrane potential changes can be significantly enhanced or attenuated by a variety of pharmacological agents interfering with intracellular Ca2+ entry, ATP-dependent K+ channels opening, and Na+/Ca2+ exchanger functioning. The understanding of the ionic mechanisms underlying the differential membrane responses to ischemia represents the basis for the development of rational neuroprotective treatments during acute cerebrovascular insults.
Centonze
D
D
IRCCS Ospedale S. Lucia, Rome, Italy.
Marfia
G A
GA
Pisani
A
A
Picconi
B
B
Giacomini
P
P
Bernardi
G
G
Calabresi
P
P
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002470:Cell Survival / Q000502:physiology*; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D017072:Neostriatum / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism
D007473:Ion Channels; D018377:Neurotransmitter Agents; D017981:Receptors, Neurotransmitter