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Effects of calcium antagonists on hypoxic and NMDA injury in rat hippocampal slices
R Longo1, S Sagratella, A Scotti de Carolis
1Pharmacology Department, Istituto Superiore di Sanità, Roma, Italy.
Abstract:
The effects of various calcium antagonists, acting at the different neuronal calcium channels, were studied towards two models of in vitro neuronal injury in rat hippocampal slices. In particular, the influence of the drugs were tested on the electrical failure induced by treatment of hippocampal slices with hypoxia or high concentrations of the excitatory amino acid N-methyl-D-aspartate (NMDA). The L-type calcium antagonists, nifedipine (100 microM) and diltiazem (100 microM) or the T-type calcium antagonist amiloride (100 microM) failed to significantly affect the recovery from the CA1 electrical failure induced by both hypoxia or NMDA (50 microM). The N-type calcium antagonists, omega-conotoxin GVIA (0.5 microM) and neomycin (300 microM) significantly (P < 0.01) increased the probability of the recovery of the CA1 population spike after hypoxia but not after NMDA (50 microM). The glutamate antagonist dizocilipine (50 microM), tested for comparison, significantly (P < 0.01) increased the probability of the recovery of the CA1 population spike after hypoxia and NMDA (50 microM). The results suggest an involvement of calcium channels especially of N-type in the genesis of hypoxic but not NMDA neuronal injury.
Insights
N-type calcium channel blockers aided recovery from hypoxic neuronal injury in rat hippocampus slices. However, they did not protect against N-methyl-D-aspartate induced injury, suggesting specific roles in hypoxic damage.
Area of Science:
- Neuroscience
- Pharmacology
- Cellular Biology
Background:
- Neuronal injury models are crucial for understanding brain damage.
- Calcium channels play a significant role in neuronal function and injury.
Purpose of the Study:
- To investigate the effects of various calcium antagonists on in vitro neuronal injury models.
- To determine the specific roles of different neuronal calcium channels in hypoxic and N-methyl-D-aspartate (NMDA) induced injury.
Main Methods:
- Utilized rat hippocampal slices for in vitro studies.
- Induced neuronal injury using hypoxia and NMDA exposure.
- Administered various calcium antagonists: L-type (nifedipine, diltiazem), T-type (amiloride), N-type (omega-conotoxin GVIA, neomycin), and a glutamate antagonist (dizocilipine).
- Assessed recovery of the CA1 population spike.
Main Results:
- L-type and T-type calcium antagonists did not significantly affect recovery from hypoxia or NMDA-induced injury.
- N-type calcium antagonists significantly improved recovery after hypoxia but not NMDA exposure.
- The glutamate antagonist dizocilipine enhanced recovery from both hypoxia and NMDA-induced injury.
Conclusions:
- N-type calcium channels are implicated in the mechanisms of hypoxic neuronal injury.
- NMDA-induced neuronal injury may involve different pathways not significantly modulated by N-type calcium antagonists.
- Findings highlight the differential involvement of calcium channel subtypes in various neuronal injury models.