Abstract
T-type Ca(2+) currents have been proposed to be involved in the genesis of spike-and-wave discharges, a sign of absence seizures, but direct evidence in vivo to support this hypothesis has been lacking. To address this question, we generated a null mutation of the alpha(1G) subunit of T-type Ca(2+) channels. The thalamocortical relay neurons of the alpha(1G)-deficient mice lacked the burst mode firing of action potentials, whereas they showed the normal pattern of tonic mode firing. The alpha(1G)-deficient thalamus was specifically resistant to the generation of spike-and-wave discharges in response to GABA(B) receptor activation. Thus, the modulation of the intrinsic firing pattern mediated by alpha(1G) T-type Ca(2+) channels plays a critical role in the genesis of absence seizures in the thalamocortical pathway.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
4-Butyrolactone / pharmacology
-
Animals
-
Baclofen / pharmacology
-
Calcium Channels, T-Type / deficiency
-
Calcium Channels, T-Type / genetics
-
Calcium Channels, T-Type / physiology*
-
Cerebral Cortex / physiology*
-
Cerebral Cortex / physiopathology
-
Electroencephalography
-
Epilepsy, Absence / genetics
-
Epilepsy, Absence / physiopathology*
-
Immunity, Innate / genetics
-
Membrane Potentials / drug effects
-
Membrane Potentials / physiology
-
Mice
-
Mice, Inbred C57BL
-
Mice, Knockout
-
Neurons / drug effects
-
Neurons / physiology*
-
Protein Subunits
-
Receptors, GABA-B / physiology*
-
Seizures / genetics
-
Seizures / physiopathology*
-
Thalamic Nuclei / physiology
-
Thalamic Nuclei / physiopathology
-
Thalamus / physiology*
-
Thalamus / physiopathology
Substances
-
Calcium Channels, T-Type
-
Protein Subunits
-
Receptors, GABA-B
-
Baclofen
-
4-Butyrolactone