Functional role of TRPC proteins in vivo: lessons from TRPC-deficient mouse models.
In order to elucidate the functional role of TRPC genes, in vivo, the targeted inactivation of these genes in mice is an invaluable technique. In this review, we summarize the currently available results on the phenotype of TRPC-deficient mouse lines. The analysis of mice with targeted deletion in three TRPC genes demonstrates that these proteins represent essential constituents of agonist-activated and phospholipase C-dependent Ca2+ entry channels in primary cells. Furthermore, from the deficits observed in these TRPC-deficient mouse lines a striking number of biological functions could already be ascribed to TRPC2, TRPC4, and TRPC6, not only on the cellular level but also for complex organ functions and integrative physiology. Accordingly, TRPC2 proteins are critically involved in pheromone sensing by neurones of the vomeronasal organ and, thereby, in the regulation of sexual and social behavior of mice, TRPC4 proteins are essential determinants of endothelial-dependent regulation of vascular tone, endothelial permeability, and neurotransmitter release from thalamic interneurones, and TRPC6 proteins are supposed to have a fundamental role in the regulation of smooth muscle tone in blood vessels and lung.
Freichel
M
M
Experimentelle und Klinische Pharmakologie und Toxikologie, Univeristät des Saarlandes, D 66421 Homburg, Germany. marc.freichel@uniklinik-saarland.de
Vennekens
R
R
Olausson
J
J
Hoffmann
M
M
Müller
C
C
Stolz
S
S
Scheunemann
J
J
Weissgerber
P
P
Flockerzi
V
V
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel
D015220:Calcium Channels; D008565:Membrane Proteins; D050052:TRPC Cation Channels; C489571:TRPC4 ion channel; D000074287:TRPC6 Cation Channel; C491858:Trpc2 protein, mouse; C492146:Trpc6 protein, mouse; D002118:Calcium