PMID- 11113149
OWN - NLM
STAT- MEDLINE
DCOM- 20010621
LR  - 20220225
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 276
IP  - 11
DP  - 2001 Mar 16
TI  - Properties of a native cation channel activated by Ca2+ store depletion in 
      vascular smooth muscle cells.
PG  - 7782-90
AB  - Depletion of intracellular Ca(2+) stores activates capacitative Ca(2+) influx in 
      smooth muscle cells, but the native store-operated channels that mediate such 
      influx remain unidentified. Recently we demonstrated that calcium influx factor 
      produced by yeast and human platelets with depleted Ca(2+) stores activates small 
      conductance cation channels in excised membrane patches from vascular smooth 
      muscle cells (SMC). Here we characterize these channels in intact cells and 
      present evidence that they belong to the class of store-operated channels, which 
      are activated upon passive depletion of Ca(2+) stores. Application of 
      thapsigargin (TG), an inhibitor of sarco-endoplasmic reticulum Ca(2+) ATPase, to 
      individual SMC activated single 3-pS cation channels in cell-attached membrane 
      patches. Channels remained active when inside-out membrane patches were excised 
      from the cells. Excision of membrane patches from resting SMC did not by itself 
      activate the channels. Loading SMC with BAPTA 
      (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid), which slowly depletes 
      Ca(2+) stores without a rise in intracellular Ca(2+), activated the same 3-pS 
      channels in cell-attached membrane patches as well as whole cell nonselective 
      cation currents in SMC. TG- and BAPTA-activated 3-pS channels were 
      cation-selective but poorly discriminated among Ca(2+), Sr(2+), Ba(2+), Na(+), 
      K(+), and Cs(+). Open channel probability did not change at negative membrane 
      potentials but increased significantly at high positive potentials. Activation of 
      3-pS channels did not depend on intracellular Ca(2+) concentration. Neither TG 
      nor a variety of second messengers (including Ca(2+), InsP3, InsP4, GTPgammaS, 
      cyclic AMP, cyclic GMP, ATP, and ADP) activated 3-pS channels in inside-out 
      membrane patches. Thus, 3-pS nonselective cation channels are present and 
      activated by TG or BAPTA-induced depletion of intracellular Ca(2+) stores in 
      intact SMC. These native store-operated cation channels can account for 
      capacitative Ca(2+) influx in SMC and can play an important role in regulation of 
      vascular tone.
FAU - Trepakova, E S
AU  - Trepakova ES
AD  - Vascular Biology Unit, Department of Medicine, Boston University School of 
      Medicine, Boston, Massachusetts 02118, USA.
FAU - Gericke, M
AU  - Gericke M
FAU - Hirakawa, Y
AU  - Hirakawa Y
FAU - Weisbrod, R M
AU  - Weisbrod RM
FAU - Cohen, R A
AU  - Cohen RA
FAU - Bolotina, V M
AU  - Bolotina VM
LA  - eng
GR  - HL07224/HL/NHLBI NIH HHS/United States
GR  - HL54150/HL/NHLBI NIH HHS/United States
GR  - HL55993/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20001211
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Ion Channels)
RN  - 526U7A2651 (Egtazic Acid)
RN  - 67526-95-8 (Thapsigargin)
RN  - K22DDW77C0 (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Aorta/drug effects/metabolism
MH  - Calcium/*metabolism
MH  - Cells, Cultured
MH  - Dogs
MH  - Egtazic Acid/analogs & derivatives/pharmacology
MH  - Ion Channels/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Muscle, Smooth, Vascular/cytology/*metabolism
MH  - Rabbits
MH  - Thapsigargin/pharmacology
MH  - Vasoconstriction/drug effects
EDAT- 2000/12/13 00:00
MHDA- 2001/06/22 10:01
CRDT- 2000/12/13 00:00
PHST- 2000/12/13 00:00 [pubmed]
PHST- 2001/06/22 10:01 [medline]
PHST- 2000/12/13 00:00 [entrez]
AID - S0021-9258(19)32116-7 [pii]
AID - 10.1074/jbc.M010104200 [doi]
PST - ppublish
SO  - J Biol Chem. 2001 Mar 16;276(11):7782-90. doi: 10.1074/jbc.M010104200. Epub 2000 
      Dec 11.