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Vol. 58, Issue 1, 98-108, July 2000
Washington University School of Medicine, Department of
Anesthesiology, St. Louis, Missouri (S.M.T., C.J.L.) and Department of
Pharmacology, University of Virginia, Charlottesville, Virginia
(E.P.-R.)
The sensitivity to anticonvulsants and anesthetics of Ca2+
currents arising from 
1G and 1H subunits was examined in stably transfected HEK293 cells. For comparison, in some cases blocking effects on dorsal root ganglion (DRG) T currents were also examined under identical ionic conditions. The anticonvulsant, phenytoin, which
partially blocks DRG T current, blocked 1G current completely but
with weaker affinity (~140 µM). Among different cells, 1H current exhibited either of two responses to phenytoin. In one subpopulation of cells, phenytoin produced a partial, higher affinity block (IC50 ~7.2 µM, maximum block ~43%) similar to
that in DRG neurons. In other cells, phenytoin produced complete, but
lower affinity, blockade (IC50 ~138 µM, maximum block
~89%). Another anticonvulsant, -methyl--phenylsuccinimide
(MPS), blocked DRG current partially, but blocked both 1G and 1H
currents completely with weaker affinity (~1.7 mM). These data
suggest that higher affinity blockade of T-type currents by phenytoin
and MPS may require additional regulatory factors that can contribute
to native T-type channels. In contrast, anesthetics blocked all T
current variants similarly and completely. Block of 1G current by
anesthetics had the following order of potency: propofol
(IC50 ~20.5 µM) > etomidate (~161 µM) = octanol (~160 µM) > isoflurane (~277 µM) > ketamine
(~1.2 mM), comparable with results on DRG T currents. Barbiturates completly blocked 1G currents with potency [thiopental (~280 µM), pentobarbital (~310 µM), phenobarbital (~1.54
mM)] similar to that in DRG cells. The effects of propofol, octanol, and pentobarbital on 1H currents were indistinguishable from effects
on 1G currents.
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