PMID- 11600493
OWN - NLM
STAT- MEDLINE
DCOM- 20020131
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 276
IP  - 51
DP  - 2001 Dec 21
TI  - Expression of Trp3 determines sensitivity of capacitative Ca2+ entry to nitric 
      oxide and mitochondrial Ca2+ handling: evidence for a role of Trp3 as a subunit 
      of capacitative Ca2+ entry channels.
PG  - 48149-58
AB  - The role of Trp3 in cellular regulation of Ca(2+) entry by NO was studied in 
      human embryonic kidney (HEK) 293 cells. In vector-transfected HEK293 cells 
      (controls), thapsigargin (TG)-induced (capacitative Ca(2+) entry (CCE)-mediated) 
      intracellular Ca(2+) signals and Mn(2+) entry were markedly suppressed by the NO 
      donor 2-(N,N-diethylamino)diazenolate-2-oxide sodium salt (3 microm) or by 
      authentic NO (100 microm). In cells overexpressing Trp3 (T3-9), TG-induced 
      intracellular Ca(2+) signals exhibited an amplitude similar to that of controls 
      but lacked sensitivity to inhibition by NO. Consistently, NO inhibited TG-induced 
      Mn(2+) entry in controls but not in T3-9 cells. Moreover, CCE-mediated Mn(2+) 
      entry into T3-9 cells exhibited a striking sensitivity to inhibition by 
      extracellular Ca(2+), which was not detectable in controls. Suppression of 
      mitochondrial Ca(2+) handling with the uncouplers carbonyl cyanide m-chlorophenyl 
      hydrazone (300 nm) or antimycin A(1) (-AA(1)) mimicked the inhibitory effect of 
      NO on CCE in controls but barely affected CCE in T3-9 cells. T3-9 cells exhibited 
      enhanced carbachol-stimulated Ca(2+) entry and clearly detectable cation currents 
      through Trp3 cation channels. NO as well as carbonyl cyanide m-chlorophenyl 
      hydrazone slightly promoted carbachol-induced Ca(2+) entry into T3-9 cells. 
      Simultaneous measurement of cytoplasmic Ca(2+) and membrane currents revealed 
      that Trp3 cation currents are inhibited during Ca(2+) entry-induced elevation of 
      cytoplasmic Ca(2+), and that this negative feedback regulation is blunted by NO. 
      Our results demonstrate that overexpression of Trp3 generates phospholipase 
      C-regulated cation channels, which exhibit regulatory properties different from 
      those of endogenous CCE channels. Moreover, we show for the first time that Trp3 
      expression determines biophysical properties as well as regulation of CCE 
      channels by NO and mitochondrial Ca(2+) handling. Thus, we propose Trp3 as a 
      subunit of CCE channels.
FAU - Thyagarajan, B
AU  - Thyagarajan B
AD  - Department of Pharmacology and Toxicology, Karl Franzens University, Graz A-8010, 
      Austria.
FAU - Poteser, M
AU  - Poteser M
FAU - Romanin, C
AU  - Romanin C
FAU - Kahr, H
AU  - Kahr H
FAU - Zhu, M X
AU  - Zhu MX
FAU - Groschner, K
AU  - Groschner K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20011012
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Calcium Channels)
RN  - 0 (Diethylamines)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (Nitrogen Oxides)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 11118-72-2 (antimycin)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 555-60-2 (Carbonyl Cyanide m-Chlorophenyl Hydrazone)
RN  - 642-15-9 (Antimycin A)
RN  - 67526-95-8 (Thapsigargin)
RN  - 92818-79-6 (diethylamine dinitric oxide adduct)
RN  - EC 4.1.1.48 (Indole-3-Glycerol-Phosphate Synthase)
RN  - EC 4.1.3.27 (Anthranilate Synthase)
RN  - EC 4.1.3.27 (TRP3 protein, S cerevisiae)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Anthranilate Synthase/*metabolism
MH  - Antimycin A/*analogs & derivatives/pharmacology
MH  - Calcium/*metabolism
MH  - Calcium Channels/chemistry/*metabolism
MH  - Carbonyl Cyanide m-Chlorophenyl Hydrazone/pharmacology
MH  - Cell Line
MH  - Diethylamines/pharmacology
MH  - Humans
MH  - Indole-3-Glycerol-Phosphate Synthase/*metabolism
MH  - Mitochondria/drug effects/*metabolism
MH  - Multienzyme Complexes/*metabolism
MH  - Nitric Oxide/*metabolism
MH  - Nitrogen Oxides
MH  - *Saccharomyces cerevisiae Proteins
MH  - Thapsigargin/pharmacology
EDAT- 2001/10/16 10:00
MHDA- 2002/02/01 10:01
CRDT- 2001/10/16 10:00
PHST- 2001/10/16 10:00 [pubmed]
PHST- 2002/02/01 10:01 [medline]
PHST- 2001/10/16 10:00 [entrez]
AID - S0021-9258(19)40329-3 [pii]
AID - 10.1074/jbc.M103977200 [doi]
PST - ppublish
SO  - J Biol Chem. 2001 Dec 21;276(51):48149-58. doi: 10.1074/jbc.M103977200. Epub 2001 
      Oct 12.