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The effects of chemically and electrically-induced convulsions on [3H]nitrendipine binding in mouse brain
1Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona.
Abstract:
The effects of chemically and electrically-evoked seizures on [3H]nitrendipine binding to voltage-dependent calcium channels in mouse brain were determined 30 and 60 min following the initiation of convulsions. While maximal electroconvulsive shock, pentylenetetrazol and strychnine exhibited either no or marginal effects, Ro 5-4864 produced a decrease (14%) in the Bmax of [3H]nitrendipine at 30 min but not 60 min. The convulsant dihydropyridine calcium channel activator, BAY K 8644, produced a significant increase in the Kd (31%) of [3H]nitrendipine at 30 min, and a significant increase in both the Bmax (21%) and Kd (28%) of [3H]nitrendipine 60 min following the initiation of convulsions. While maximal electroconvulsive shock, pentylenetetrazol and strychnine exhibited either no or marginal effects, Ro 5-4864 produced a decrease (14%) in the Bmax of [3H]nitrendipine at 30 min but not 60 min following the initiation of convulsions. These findings indicate that modulation of voltage-dependent calcium channels by certain convulsants may be important in the genesis of seizures or in post-ictal compensatory processes.
Insights
Certain convulsants alter voltage-dependent calcium channels in the mouse brain. BAY K 8644 significantly affected [3H]nitrendipine binding, suggesting a role in seizure mechanisms or recovery.
Area of Science:
- Neuropharmacology
- Neurochemistry
- Epilepsy Research
Background:
- Voltage-dependent calcium channels (VDCCs) play critical roles in neuronal excitability.
- Seizures involve complex alterations in neuronal activity and neurotransmission.
- Nitrendipine is a dihydropyridine that binds to L-type VDCCs.
Purpose of the Study:
- To investigate the impact of chemically and electrically-induced seizures on [3H]nitrendipine binding to VDCCs in the mouse brain.
- To determine if specific convulsants modulate VDCCs during or after seizure activity.
Main Methods:
- Mice were subjected to chemically-induced seizures (Ro 5-4864, pentylenetetrazol, strychnine) or electrically-induced seizures (maximal electroconvulsive shock).
- A specific convulsant dihydropyridine calcium channel activator, BAY K 8644, was also administered.
- Binding assays for [3H]nitrendipine to VDCCs were performed at 30 and 60 minutes post-seizure initiation.
- Analysis of binding parameters, including Bmax (maximum binding) and Kd (dissociation constant).
Main Results:
- Maximal electroconvulsive shock, pentylenetetrazol, and strychnine showed minimal effects on [3H]nitrendipine binding.
- Ro 5-4864 caused a 14% decrease in Bmax at 30 minutes, but not at 60 minutes.
- BAY K 8644 significantly increased Kd by 31% at 30 minutes.
- BAY K 8644 also significantly increased both Bmax (21%) and Kd (28%) at 60 minutes post-convulsions.
Conclusions:
- Specific convulsants, particularly BAY K 8644, can modulate voltage-dependent calcium channels.
- These modulations may be involved in the underlying mechanisms of seizure generation.
- Changes in VDCC binding could represent compensatory processes occurring after seizure activity.