Cerebral vasospasm (CVS) is the most treatable component of
subarachnoid hemorrhage (SAH), which can be reduced by
endothelin receptor antagonists.
Endothelin-evoked vasospasm is considered to be mediated by Ca(2+) influx in the smooth muscle through voltage-dependent Ca(2+) channel (
VDCC) and nonselective
cation channels (NSCC). Because
VDCC antagonists such as
nimodipine have been shown to be relatively less effective than the
endothelin receptor antagonists, it is assumed that NSCC maybe a more important component in mediating Ca(2+) influx during CVS. In this study, we used the basilar arteries from a "two-
hemorrhage" rat model of SAH to investigate expressions of
transient receptor potential channel 1 (TRPC1),
transient receptor potential channel 3 (TRPC3) and
stromal interaction molecule 1 (STIM1), which are considered as the promising candidates constituting NSCC. To investigate the possible role of NSCC in phenotypic switching, we performed immunohistochemical staining to examine expressions of SMα-actin and
PCNA, markers of smooth muscle phenotypic switching. We found that the basilar arteries exhibited vasospasm after SAH and that vasospasm became more severe on days 5 and 7 after SAH. Elevated
mRNA and
protein expressions of TRPC1 and STIM1 were detected after SAH and peaked on days 5 and 7, which was in a parallel time course to the development of
cerebral vasospasm. The
mRNA and
protein expressions of TRPC3 were not changed in the SAH group when compared with those in the control. Results of immunohistochemical staining with anti-
PCNA and anti-SMα-actin
antibodies also showed enhanced expression of
PCNA and disappearance of SMα-actin from day 1 to day 7. Taken together, the above results supported a novel mechanism that the components of store-operated
calcium channels, TRPC1 and STIM1 mediated the Ca(2+) influx and phenotypic switching in smooth muscle cells, which promoted the development of vasospasm after SAH. TRPC3, which is a component of receptor-operated
calcium channels, was not involved in the above-mentioned mechanism.