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Calcium currents in acutely isolated human neocortical neurons
R J Sayer1, A M Brown, P C Schwindt
1Department of Physiology and Biophysics, University of Washington, Seattle 98195.
Journal of Neurophysiology
|May 1, 1993
Summary
Human temporal neocortex neurons exhibit distinct calcium (Ca2+) currents, similar to rats but with less T-type current. Antiepileptic drugs showed minimal impact on these essential neuronal currents.
Area of Science:
- Neuroscience
- Neurophysiology
- Pharmacology
Background:
- Calcium (Ca2+) currents are crucial for neuronal function, including neurotransmitter release and excitability.
- Understanding Ca2+ channel subtypes and their modulation is vital for neurological research and drug development.
- Human neocortical neurons provide a direct model for studying these currents in the context of human brain function.
Purpose of the Study:
- To characterize Ca2+ currents in adult human temporal neocortical neurons.
- To compare these currents with those found in animal models.
- To investigate the effects of dihydropyridine Ca2+ antagonists and common antiepileptic drugs on these currents.
Main Methods:
- Whole-cell voltage-clamp recordings were performed on acutely isolated human temporal neocortical pyramidal neurons.
- Neurons were obtained from patients undergoing surgery for intractable epilepsy.
- Pharmacological agents, including omega-conotoxin GVIA, nifedipine, nimodipine, ethosuximide, carbamazepine, valproate, and phenytoin, were used to probe Ca2+ current properties.
Main Results:
- Two main Ca2+ current components were identified: a low-threshold transient (T-type) and a high-threshold slowly inactivating current.
- Human neocortical Ca2+ currents showed similarities to rat neocortical neurons, with T-type currents being less prominent.
- Dihydropyridine antagonists (nifedipine, nimodipine) blocked a significant portion of the high-threshold current, suggesting L-type channels. Antiepileptic drugs had minimal effects at therapeutic concentrations, with phenytoin showing a slight reduction.
Conclusions:
- Human temporal neocortical neurons possess distinct low- and high-threshold Ca2+ currents.
- These currents share similarities with those in rodent models, but with quantitative differences.
- The study does not support the hypothesis that inhibition of these Ca2+ currents is a primary mechanism of action for the tested antiepileptic drugs.