Pressure-induced and store-operated cation influx in vascular smooth muscle cells is independent of TRPC1.
Among the classical transient receptor potential (TRPC) subfamily, TRPC1 is described as a mechanosensitive and store-operated channel proposed to be activated by hypoosmotic cell swelling and positive pipette pressure as well as regulated by the filling status of intracellular Ca(2+) stores. However, evidence for a physiological role of TRPC1 may most compellingly be obtained by the analysis of a TRPC1-deficient mouse model. Therefore, we have developed and analyzed TRPC1(-/-) mice. Pressure-induced constriction of cerebral arteries was not impaired in TRPC1(-/-) mice. Smooth muscle cells from cerebral arteries activated by hypoosmotic swelling and positive pipette pressure showed no significant differences in cation currents compared to wild-type cells. Moreover, smooth muscle cells of TRPC1(-/-) mice isolated from thoracic aortas and cerebral arteries showed no change in store-operated cation influx induced by thapsigargin, inositol-1,4,5 trisphosphate, and cyclopiazonic acid compared to cells from wild-type mice. In contrast to these results, small interference RNAs decreasing the expression of stromal interaction molecule 1 (STIM1) inhibited thapsigargin-induced store-operated cation influx, demonstrating that STIM1 and TRPC1 are mutually independent. These findings also imply that, as opposed to current concepts, TRPC1 is not an obligatory component of store-operated and stretch-activated ion channel complexes in vascular smooth muscle cells.
Dietrich
Alexander
A
Institut für Pharmakologie und Toxikologie, Philipps-Universität Marburg, Marburg, Germany. dietrica@staff.uni-marburg.de
Kalwa
Hermann
H
Storch
Ursula
U
Mederos y Schnitzler
Michael
M
Salanova
Birgit
B
Pinkenburg
Olaf
O
Dubrovska
Galyna
G
Essin
Kirill
K
Gollasch
Maik
M
Birnbaumer
Lutz
L
Gudermann
Thomas
T
D000595:Amino Acid Sequence; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D001483:Base Sequence; D015220:Calcium Channels; D002536:Cerebral Arteries / Q000166:cytology; D007211:Indoles / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051379:Mice; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D000071737:Stromal Interaction Molecule 1; D050052:TRPC Cation Channels / Q000172:deficiency / Q000502:physiology*; D019284:Thapsigargin / Q000494:pharmacology
D015220:Calcium Channels; D007211:Indoles; D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; C100757:Stim1 protein, mouse; D000071737:Stromal Interaction Molecule 1; D050052:TRPC Cation Channels; C096351:transient receptor potential cation channel, subfamily C, member 1; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; C000543:cyclopiazonic acid