Skip Navigation


BJA Advance Access originally published online on June 20, 2009
British Journal of Anaesthesia 2009 103(2):244-254; doi:10.1093/bja/aep107
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
103/2/244    most recent
aep107v1
Right arrow E-Letters: Submit a response to the article
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Chen, B.-S.
Right arrow Articles by Wu, S.-N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chen, B.-S.
Right arrow Articles by Wu, S.-N.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?


© The Author [2009]. Published by Oxford University Press on behalf of The Board of Directors of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournal.org

Dexmedetomidine, an {alpha}2-adrenergic agonist, inhibits neuronal delayed-rectifier potassium current and sodium current

B.-S. Chen1,3, H. Peng2 and S.-N. Wu1,2,*

1 Institute of Basic Medical Sciences
2 Department of Physiology, National Cheng Kung University Medical College, No. 1, University Road, Tainan 70101, Taiwan, Republic of China
3 Department of Anesthesiology, Buddhist Dalin Tzu Chi General Hospital, Chiayi County, Taiwan, Republic of China

* Corresponding author. E-mail: snwu{at}mail.ncku.edu.tw

Background: Dexmedetomidine (DEX), a selective agonist of {alpha}2-adrenergic receptors, is recognized to facilitate analgesia and anaesthesia in humans. Despite the potential for wide use, its effects on ion currents and membrane potential in neurones remain largely unclear.

Methods: We investigated the effects of DEX on ion channels in NG108-15 neuronal cells differentiated with dibutyryl cyclic AMP and in cultured cerebellar neurones.

Results: DEX suppressed the amplitude of delayed rectifier K+ current [IK(DR)] in a concentration-dependent manner with an IC50 value of 4.6 µM in NG108-15 cells. No change in the steady-state inactivation of IK(DR) was evident in the presence of DEX. A minimal binding scheme was also used to evaluate DEX-induced block of IK(DR). Inhibition of IK(DR) by DEX was still observed in cells preincubated with yohimbine (10 µM) or efaroxan (10 µM). DEX depressed the peak amplitude of Na+ current (INa), whereas it had minimal effect on L-type Ca2+ current. Under current-clamp configuration, DEX increased the duration of action potentials (APs). IK(DR) and INa in response to AP waveforms were more sensitive to block by DEX than those elicited during rectangular pulses. In isolated cerebellar granule cells, DEX also effectively suppressed IK(DR).

Conclusions: The effects of DEX are not limited to its interactions with {alpha}2-adrenergic receptors. Inhibitory effects on IK(DR) and INa constitute one of the underlying mechanisms through which DEX and its structurally related compounds might affect neuronal activity in vivo.

Keywords: ions, ion channels, pharmacology; ions, ion channels, voltage-gated; model, neuroblastoma cells; pharmacology, dexmedetomidine


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.