Agonist-evoked calcium entry in vascular smooth muscle cells requires IP(3) receptor-mediated activation of TRPC1.
(2008) European Journal of Pharmacology — Vol. 583, n° 1, p. 135-147 (2008)
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- Transient receptor potential canonical (TRPC) proteins have been proposed to function as plasma membrane Ca(2+) channels activated by store depletion and/or by receptor stimulation. However, their role in the increase in cytosolic Ca(2+) activated by contractile agonists in vascular smooth muscle is not yet elucidated. The present study was designed to investigate the functional and molecular properties of the Ca(2+) entry pathway activated by endothelin-1 in primary cultured aortic smooth muscle cells. Measurement of the Ca(2+) signal in fura-2-loaded cells allowed to characterize endothelin-1-evoked Ca(2+) entry, which was resistant to dihydropyridine, and was blocked by 2-aminoethoxydiphenylborate (2-APB) and micromolar concentration of Gd(3+). It was not activated by store depletion, but was inhibited by the endothelin ET(A) receptor antagonist BQ-123, and by heparin. On the opposite, thapsigargin-induced store depletion activated a Ca(2+) entry pathway that was not affected by 2-APB, BQ-123 or heparin, and was less sensitive to Gd(3+) than was endothelin-1-evoked Ca(2+) entry. Investigation of the gene expression of TRPC isoforms by real-time RT-PCR revealed that TRPC1 was the most abundant. In cells transfected with TRPC1 small interfering RNA sequence, TRPC1 mRNA and protein expression were decreased by 72+/-3% and 86+/-2%, respectively, while TRPC6 expression was unaffected. In TRPC1 knockdown cells, both endothelin-1-evoked Ca(2+) entry and store-operated Ca(2+) entry evoked by thapsigargin were blunted. These results indicate that in aortic smooth muscle cells, TRPC1 is not only involved in Ca(2+) entry activated by store depletion but also in receptor-operated Ca(2+) entry, which requires inositol (1,4,5) triphosphate receptor activation.
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Tai, K., Hamaide, M.-C., Debaix, H., Gailly, P., Wibo, M., & Morel, N. (2008). Agonist-evoked calcium entry in vascular smooth muscle cells requires IP(3) receptor-mediated activation of TRPC1. European Journal of Pharmacology, 583(1), 135-147. https://doi.org/10.1016/j.ejphar.2008.01.007 (Original work published 2008)