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SBSC93
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Literature
38 records
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temporal neocortex. The aim was to compare the basic characteristics of the
currents with those previously described in animals and to examine the effects
of dihydropyridine Ca2+ antagonists and antiepileptic drugs. The tissue,
obtained from patients undergoing temporal lobe surgery for medically
intractable epilepsy, was sliced, incubated in papain, and triturated. 2. Most
of the isolated neurons (34 of 36) were judged to be pyramidal cells by their
morphology. Whole-cell voltage-clamp recordings revealed two components of
Ca2+ current: 1) a low-threshold (T-type) current that was transient, small in
amplitude, and required hyperpolarization more negative than -70 mV for
removal of inactivation and 2) a high-threshold current that was slowly
inactivating and was available for activation from more positive potentials.
The characteristics of the Ca2+ currents were very similar to those in the
neocortical neurons of young rats, although the low-threshold current was less
prominent in the human cells. 3. Subcomponents of the high-threshold current
were identified by pharmacology. About 20% of the peak current was blocked by
omega-conotoxin GVIA (presumed N current) and 40-50% of the peak current was
blocked by micromolar concentrations of the dihydropyridine Ca2+ antagonists
nifedipine and nimodipine (presumed L current). In two neurons tested with a
range of nimodipine concentrations, the threshold for suppression of the
high-threshold current was approximately 10 nM. 4. The antiepileptic agents
ethosuximide, carbamazepine, and valproate did not affect the Ca2+ currents at
therapeutically relevant concentrations. Phenytoin marginally reduced the low-
and high-threshold Ca2+ currents at 8 microM (a concentration corresponding to
the upper therapeutic range). The results do not support the hypothesis that
inhibition of Ca2+ currents in neocortical pyramidal neurons is a major action
of these drugs.
