Lack of the burst firing of thalamocortical relay neurons and resistance to absence seizures in mice lacking alpha(1G) T-type Ca(2+) channels.
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.
Kim
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National Creative Research Initiative Center, for Calcium and Learning, Department of Life Science, Pohang University of Science and Technology, 790-784, Pohang, South Korea. shin@kist.re.kr
Song
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Keum
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Lee
T
T
Jeong
M J
MJ
Kim
S S
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McEnery
M W
MW
Shin
H S
HS
D015107:4-Butyrolactone / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D020747:Calcium Channels, T-Type / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002540:Cerebral Cortex / Q000502:physiology* / Q000503:physiopathology; D004569:Electroencephalography; D004832:Epilepsy, Absence / Q000235:genetics / Q000503:physiopathology*; D007113:Immunity, Innate / Q000235:genetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D021122:Protein Subunits; D018080:Receptors, GABA-B / Q000502:physiology*; D012640:Seizures / Q000235:genetics / Q000503:physiopathology*; D013787:Thalamic Nuclei / Q000502:physiology / Q000503:physiopathology; D013788:Thalamus / Q000502:physiology* / Q000503:physiopathology
D020747:Calcium Channels, T-Type; D021122:Protein Subunits; D018080:Receptors, GABA-B; D001418:Baclofen; D015107:4-Butyrolactone