Diurnal gene expression patterns of T-type calcium channels and their modulation by ethanol.
The transient (T-type) calcium channel participates in the generation of normal brain rhythms as well as abnormal rhythms associated with a range of neurological disorders. There are three different isoforms of T-type channels and all are particularly enriched in the thalamus, which is involved in generating many of these rhythms. We report a novel means of T-type channel regulation in the thalamus that involves diurnal regulation of gene expression. Using real time polymerase chain reaction we detected a diurnal pattern of gene expression for all T-type channel transcripts. The peak of gene expression for the CaV3.1 transcript occurred close to the transition from active to inactive (sleep) states, while expression for both CaV3.2 and CaV3.3 peaked near the transition of inactive to active phase. We assessed the effect of chronic consumption of ethanol on these gene expression patterns by examining thalamic tissues of ethanol-consuming cohorts that were housed with the controls, but which received ethanol in the form of a liquid diet. Ethanol consumption resulted in a significant shift of peak gene expression of approximately 5 h for CaV3.2 toward the normally active phase of the mice, as well as increasing the overall gene expression levels by approximately 1.7-fold. Peak gene expression was significantly increased for both CaV3.2 and CaV3.3. Measurements of CaV3.3 protein expression reflected increases in gene expression due to ethanol. Our results illustrate a novel regulatory mechanism for T-type calcium channels that is consistent with their important role in generating thalamocortical sleep rhythms, and suggests that alterations in the pattern of gene expression of these channels could contribute to the disruption of normal sleep by ethanol.
Nordskog
B K
BK
Department of Neurobiology and Anatomy, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
Hammarback
J A
JA
Godwin
D W
DW
D000704:Analysis of Variance; D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D020747:Calcium Channels, T-Type / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D002492:Central Nervous System Depressants / Q000097:blood / Q000494:pharmacology*; D002940:Circadian Rhythm / Q000187:drug effects* / Q000502:physiology; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013788:Thalamus / Q000187:drug effects
D020747:Calcium Channels, T-Type; D002492:Central Nervous System Depressants; D012333:RNA, Messenger; D000431:Ethanol