PMID- 21035852
OWN - NLM
STAT- MEDLINE
DCOM- 20110217
LR  - 20191210
IS  - 1532-1991 (Electronic)
IS  - 0143-4160 (Linking)
VI  - 48
IP  - 5
DP  - 2010 Nov
TI  - Stretch-activated channels in pulmonary arterial smooth muscle cells from 
      normoxic and chronically hypoxic rats.
PG  - 251-9
LID - 10.1016/j.ceca.2010.09.011 [doi]
AB  - Stretch-activated channels (SACs) act as membrane mechanotransducers since they 
      convert physical forces into biological signals and hence into a cell response. 
      Pulmonary arterial smooth muscle cells (PASMCs) are continuously exposed to 
      mechanical stimulations e.g., compression and stretch, that are enhanced under 
      conditions of pulmonary arterial hypertension (PAH). Using the patch-clamp 
      technique (cell-attached configuration) in PASMCs, we showed that applying graded 
      negative pressures (from 0 to -60 mmHg) to the back end of the patch pipette 
      increases occurrence and activity of SACs. The current-voltage relationship (from 
      -80 to +40 mV) was almost linear with a reversal potential of 1 mV and a slope 
      conductance of 34 pS. SACs were inhibited in the presence of GsMTx-4, a specific 
      SACs blocker. Using microspectrofluorimetry (indo-1), we found that 
      hypotonic-induced cell swelling increases intracellular Ca(2+) concentration 
      ([Ca(2+)](i)). This [Ca(2+)](i) increase was markedly inhibited in the absence of 
      external Ca(2+) or in the presence of the following blockers of SACs: gadolinium, 
      streptomycin, and GsMTx-4. Interestingly, in chronically hypoxic rats, an animal 
      model of PAH, SACs were more active and hypotonic-induced calcium response in 
      PASMCs was significantly higher (nearly a two-fold increase). Moreover, unlike in 
      normoxic rats, intrapulmonary artery rings from hypoxic rats mounted in a Mulvany 
      myograph, exhibited a myogenic tone sensitive to SAC blockers. In conclusion, 
      this work demonstrates that SACs in rat PASMCs can be activated by membrane 
      stretch as well as hypotonic stimulation and are responsible for [Ca(2+)](i) 
      increase. The link between SACs activation-induced calcium response and myogenic 
      tone in chronically hypoxic rats suggests that SACs are an important element for 
      the increased pulmonary vascular tone in PAH and that they may represent a 
      molecular target for PAH treatment.
CI  - Copyright (c) 2010 Elsevier Ltd. All rights reserved.
FAU - Ducret, Thomas
AU  - Ducret T
AD  - Universite Bordeaux 2, Laboratoire de Physiologie Cellulaire Respiratoire, 
      F-33076 Bordeaux, France. thomas.ducret@u-bordeaux2.fr
FAU - El Arrouchi, Jalila
AU  - El Arrouchi J
FAU - Courtois, Arnaud
AU  - Courtois A
FAU - Quignard, Jean-Francois
AU  - Quignard JF
FAU - Marthan, Roger
AU  - Marthan R
FAU - Savineau, Jean-Pierre
AU  - Savineau JP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101029
PL  - Netherlands
TA  - Cell Calcium
JT  - Cell calcium
JID - 8006226
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Calcium Channels)
RN  - 0 (Hypotonic Solutions)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (MTx4 protein, Grammostola spatulata)
RN  - 0 (Peptides)
RN  - 0 (Spider Venoms)
RN  - AU0V1LM3JT (Gadolinium)
RN  - SY7Q814VUP (Calcium)
RN  - Y45QSO73OB (Streptomycin)
SB  - IM
MH  - Animals
MH  - Calcium/metabolism
MH  - Calcium Channel Blockers/pharmacology
MH  - Calcium Channels/metabolism/*physiology
MH  - Cells, Cultured
MH  - Familial Primary Pulmonary Hypertension
MH  - Gadolinium/pharmacology
MH  - Hypertension, Pulmonary/metabolism/physiopathology
MH  - Hypotonic Solutions
MH  - Hypoxia/metabolism/*physiopathology
MH  - Intercellular Signaling Peptides and Proteins
MH  - Male
MH  - Mechanotransduction, Cellular
MH  - Membrane Potentials/drug effects/physiology
MH  - Muscle, Smooth, Vascular/metabolism/*physiology/physiopathology
MH  - Myocytes, Smooth Muscle/metabolism/*physiology
MH  - Patch-Clamp Techniques
MH  - Peptides/pharmacology
MH  - Pressoreceptors/drug effects/metabolism/*physiology
MH  - Pulmonary Artery/metabolism/*physiology/physiopathology
MH  - Rats
MH  - Spider Venoms/pharmacology
MH  - Streptomycin/pharmacology
EDAT- 2010/11/03 06:00
MHDA- 2011/02/18 06:00
CRDT- 2010/11/02 06:00
PHST- 2010/02/19 00:00 [received]
PHST- 2010/09/10 00:00 [revised]
PHST- 2010/09/30 00:00 [accepted]
PHST- 2010/11/02 06:00 [entrez]
PHST- 2010/11/03 06:00 [pubmed]
PHST- 2011/02/18 06:00 [medline]
AID - S0143-4160(10)00147-8 [pii]
AID - 10.1016/j.ceca.2010.09.011 [doi]
PST - ppublish
SO  - Cell Calcium. 2010 Nov;48(5):251-9. doi: 10.1016/j.ceca.2010.09.011. Epub 2010 
      Oct 29.