PMID- 19128833
OWN - NLM
STAT- MEDLINE
DCOM- 20090616
LR  - 20090325
IS  - 1872-9142 (Electronic)
IS  - 0161-5890 (Linking)
VI  - 46
IP  - 7
DP  - 2009 Apr
TI  - L-type Ca2+ channels in mast cells: activation by membrane depolarization and 
      distinct roles in regulating mediator release from store-operated Ca2+ channels.
PG  - 1267-77
LID - 10.1016/j.molimm.2008.11.011 [doi]
AB  - Store-operated Ca(2+) channels (SOCs) are considered to be the principal route of 
      Ca(2+) influx in non-excitable cells. We have previously shown that in mast cells 
      IgE+antigen (Ag) induces a dihydropyridine (DHP)-sensitive Ca(2+) influx 
      independently of Ca(2+) store depletion. Since the DHP receptor is the alpha 
      subunit of L-type Ca(2+) channels (LTCCs), we examined the possible role of LTCCs 
      in mast cell activation. Mast cells exhibited substantial expression of the 
      alpha(1C) (Ca(V)1.2) subunit mRNA and protein on their cell surface. 
      IgE+Ag-induced Ca(2+) influx was substantially reduced by the LTCC inhibitor 
      nifedipine, and enhanced by the LTCC activator (S)-BayK8644, whereas these agents 
      had minimal effects on thapsigargin (TG)-induced Ca(2+) influx. These 
      LTCC-modulating agents regulated IgE+Ag-induced cell activation but not 
      TG-induced cell activation. Inhibition of SOCs by 2-aminoethoxydiphenyl borate 
      reduced both degranulation and production of cytokines, including interleukin-13 
      and tumor necrosis factor-alpha, whereas LTCC modulation reciprocally regulated 
      degranulation and cytokine production. IgE+Ag, but not TG, induced substantial 
      plasma membrane depolarization, which stimulated a DHP-sensitive Ca(2+) response. 
      Moreover, IgE+Ag-, but not TG-induced mitochondrial Ca(2+) increase was regulated 
      by LTCC modulators. Finally, gene silencing analyses using small interfering RNA 
      revealed that the alpha(1C) (Ca(V)1.2) LTCC mediated the pharmacological effects 
      of the LTCC-modulating agents. These results demonstrate that mast cells express 
      LTCCs, which becomes activated by membrane depolarization to regulate cytosolic 
      and mitochondrial Ca(2+), thereby controlling mast cell activation in a distinct 
      manner from SOCs.
FAU - Yoshimaru, Tetsuro
AU  - Yoshimaru T
AD  - Division of Molecular Cell Immunology and Allergology, Advanced Medical Research 
      Center, Nihon University Graduate School of Medical Science, 30-1 
      Oyaguchikami-cho Itabashi-ku, Tokyo 173-8610, Japan.
FAU - Suzuki, Yoshihiro
AU  - Suzuki Y
FAU - Inoue, Toshio
AU  - Inoue T
FAU - Ra, Chisei
AU  - Ra C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090106
PL  - England
TA  - Mol Immunol
JT  - Molecular immunology
JID - 7905289
RN  - 0 (Antigens)
RN  - 0 (Antigens, Surface)
RN  - 0 (Calcium Channels, L-Type)
RN  - 0 (L-type calcium channel alpha(1C))
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 67526-95-8 (Thapsigargin)
SB  - IM
MH  - Animals
MH  - Antigens/pharmacology
MH  - Antigens, Surface/metabolism/physiology
MH  - Calcium Channels, L-Type/genetics/metabolism/*physiology
MH  - Calcium Signaling/drug effects/*physiology
MH  - Cells, Cultured
MH  - Immunoglobulin E/pharmacology
MH  - Mast Cells/drug effects/*immunology/*metabolism/physiology
MH  - Membrane Potentials/drug effects/genetics/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Rats
MH  - Thapsigargin/pharmacology
EDAT- 2009/01/09 09:00
MHDA- 2009/06/17 09:00
CRDT- 2009/01/09 09:00
PHST- 2008/04/16 00:00 [received]
PHST- 2008/11/20 00:00 [revised]
PHST- 2008/11/21 00:00 [accepted]
PHST- 2009/01/09 09:00 [entrez]
PHST- 2009/01/09 09:00 [pubmed]
PHST- 2009/06/17 09:00 [medline]
AID - S0161-5890(08)00758-X [pii]
AID - 10.1016/j.molimm.2008.11.011 [doi]
PST - ppublish
SO  - Mol Immunol. 2009 Apr;46(7):1267-77. doi: 10.1016/j.molimm.2008.11.011. Epub 2009 
      Jan 6.