PMID- 20926775
OWN - NLM
STAT- MEDLINE
DCOM- 20110104
LR  - 20211203
IS  - 1522-1563 (Electronic)
IS  - 0363-6143 (Linking)
VI  - 299
IP  - 6
DP  - 2010 Dec
TI  - Inhibition of voltage-gated K+ channels in dendritic cells by rapamycin.
PG  - C1379-85
LID - 10.1152/ajpcell.00367.2010 [doi]
AB  - Rapamycin, an inhibitor of the serine/threonine kinase mammalian target of 
      rapamycin (mTOR), is a widely used immunosuppressive drug. Rapamycin affects the 
      function of dendritic cells (DCs), antigen-presenting cells participating in the 
      initiation of primary immune responses and the establishment of immunological 
      memory. Voltage-gated K(+) (Kv) channels are expressed in and impact on the 
      function of DCs. The present study explored whether rapamycin influences Kv 
      channels in DCs. To this end, DCs were isolated from murine bone marrow and ion 
      channel activity was determined by whole cell patch clamp. To more directly 
      analyze an effect of mTOR on Kv channel activity, Kv1.3 and Kv1.5 were expressed 
      in Xenopus oocytes with or without the additional expression of mTOR and 
      voltage-gated currents were determined by dual-electrode voltage clamp. As a 
      result, preincubation with rapamycin (0-50 nM) led to a gradual decline of Kv 
      currents in DCs, reaching statistical significance within 6 h and 50 nM of 
      rapamycin. Rapamycin accelerated Kv channel inactivation. Coexpression of mTOR 
      upregulated Kv1.3 and Kv1.5 currents in Xenopus oocytes. Furthermore, mTOR 
      accelerated Kv1.3 channel activation and slowed down Kv1.3 channel inactivation. 
      In conclusion, mTOR stimulates Kv channels, an effect contributing to the 
      immunomodulating properties of rapamycin in DCs.
FAU - Tyan, Leonid
AU  - Tyan L
AD  - Department of Physiology, University of Tubingen, Tubingen, Germany.
FAU - Sopjani, Mentor
AU  - Sopjani M
FAU - Dermaku-Sopjani, Miribane
AU  - Dermaku-Sopjani M
FAU - Schmid, Evi
AU  - Schmid E
FAU - Yang, Wenting
AU  - Yang W
FAU - Xuan, Nguyen Thi
AU  - Xuan NT
FAU - Shumilina, Ekaterina
AU  - Shumilina E
FAU - Lang, Florian
AU  - Lang F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101006
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Potassium Channels, Voltage-Gated)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Bone Marrow/drug effects/physiology
MH  - Dendritic Cells/*drug effects/immunology
MH  - Female
MH  - Immunosuppressive Agents/*pharmacology
MH  - Male
MH  - Membrane Potentials/drug effects/physiology
MH  - Mice
MH  - Potassium Channels, Voltage-Gated/*antagonists & inhibitors/physiology
MH  - Sirolimus/*pharmacology
MH  - TOR Serine-Threonine Kinases/physiology
EDAT- 2010/10/12 06:00
MHDA- 2011/01/05 06:00
CRDT- 2010/10/08 06:00
PHST- 2010/10/08 06:00 [entrez]
PHST- 2010/10/12 06:00 [pubmed]
PHST- 2011/01/05 06:00 [medline]
AID - ajpcell.00367.2010 [pii]
AID - 10.1152/ajpcell.00367.2010 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2010 Dec;299(6):C1379-85. doi: 
      10.1152/ajpcell.00367.2010. Epub 2010 Oct 6.