Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.14/194166
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- Title
- Inhibition of human recombinant T-type calcium channels by N-arachidonoyl 5-HT
- Related
- British journal of pharmacology, Vol. 167, Issue 5, (2012), p.1076-1088
- DOI
- 10.1111/j.1476-5381.2012.02047.x
- Publisher
- Nature Publishing Group
- Date
- 2012
- Author/Creator
- Gilmore, Andrew J
- Author/Creator
- Heblinski, Markia
- Author/Creator
- Reynolds, Aaron
- Author/Creator
- Kassiou, Michael
- Author/Creator
- Connor, Mark
- Description
- Background and purpose: N-arachidonoyl 5-HT (NA-5HT) has anti-nociceptive effects reported to be mediated by inhibitory actions at the transient receptor potential vanilloid receptor 1 (TRPV1) and fatty acid amide hydrolase (FAAH). Anandamide and N-arachidonoyl dopamine (NA-DA), endocannabinoids that activate TRPV1 or are metabolized by FAAH, also inhibit T-type calcium channels (/Ca). T-type /Ca are expressed by many excitable cells, including neurons involved in pain detection and processing. We sought to determine whether NA-5HT also modulates T-type /Ca. Experimental approach: Human recombinant T-type /Ca (Ca⌄3 channels) expressed in HEK 293 cells were examined using standard whole-cell voltage-clamp electrophysiology techniques. Key results: NA-5HT completely inhibited Ca⌄3 channels with a rank order of potency (pEC₅₀) of Ca⌄3.1(7.4)>Ca⌄3.3(6.8)≥Ca⌄3.2 (6.6). The effects of NA-5HT were voltage-dependent, and it produced significant hyperpolarizing shifts in Ca⌄3 steady-state inactivation relationships. NA-5HT selectively affected Ca⌄3.3 channel kinetics. Conclusions and implications: NA-5HT increases the steady-state inactivation of Ca⌄3 channels, reducing the number of channels available to open during depolarization. These effects occur at NA-5HT concentrations at or below those at which NA-5HT affects TRPV1 receptors and FAAH. NA-5HT is one of the most potent inhibitors of T-type /Ca described to date, and it is likely to exert some of its biological effects, including anti-nociception, via inhibition of these channels.
- Description
- 13 page(s)
- Subject Keyword
- acyl amino acid
- Subject Keyword
- anandamide
- Subject Keyword
- arachidonoyl amino acid
- Subject Keyword
- NA-5HT
- Subject Keyword
- NA-serotonin
- Subject Keyword
- nociception
- Subject Keyword
- T-type calcium channel
- Resource Type
- journal article
- Organisation
- Macquarie University. Australian School of Advanced Medicine
- Identifier
- http://hdl.handle.net/1959.14/194166
- Identifier
- ISSN:0007-1188
- Identifier
- mq_res-ext-2-s2.0-84867310203
- Language
- eng
- Reviewed
