Activation of calcium-sensing receptor increases TRPC3/6 expression in T lymphocyte in sepsis.
Sepsis is a systemic inflammatory response syndrome induced by infection. T Lymphocytes play an important role in this disease. Transient receptor potential (TRP) channels and calcium-sensing receptors (CaSR) are expressed in lymphocytes to promote intracellular Ca(2+) release. However, data about the link between CaSR and TRP channels in septic T lymphocytes are few. In this study, by Ca(2+) imaging and Western blotting, we found that in septic rat peripheral blood T lymphocytes expressions of TRPC3 and TRPC6 proteins are higher. The SR/ER Ca(2+) ATPase inhibitor thapsigargin (TG) and CaSR agonist NPS R-568 also increased expressions of TRPC3 and TRPC6 proteins, which were reversed by PLC-IP3 channel blocker U73122 and TRPC channels inhibitor SKF96365. By Ca(2+) imaging, we found that the depletion of ER Ca(2+) stores by TG elicited a transient rise in cytoplasmic Ca(2+), followed by sustained increase depending on extracellular Ca(2+). But, SKF96365, not Verapamil (L-type channels inhibitor) and NiCl2 (Na(+)/Ca(2+) exchanger inhibitor), inhibited the relatively high [Ca(2+)]i. NPS R-568 also resulted in the same effect, and the duration of [Ca(2+)]i increase was eliminated completely by U73122 and was reduced in the absence of [Ca(2+)]o. NPS R-568 and TG increased the apoptotic ratio of septic T lymphocytes, which can be suppressed by SKF96365 and U73122. These results suggested that CaSR activation promoted the expression of TRPC3 and TRPC6 and enhanced T lymphocytes apoptosis through PLC-IP3 signaling pathway in sepsis.
['Wu|Qiu-yue|QY|', 'Sun|Ming-rui|MR|', 'Wu|Chun-li|CL|', 'Li|Yang|Y|', 'Du|Jing-jing|JJ|', 'Zeng|Jing-ya|JY|', 'Bi|Hai-liang|HL|', 'Sun|Yi-hua|YH|']
D000818:Animals D017209:Apoptosis D020013:Calcium Signaling D005110:Extracellular Space D005434:Flow Cytometry D015544:Inositol 1,4,5-Trisphosphate D042541:Intracellular Space D015640:Ion Channel Gating D017208:Rats, Wistar D044169:Receptors, Calcium-Sensing D018805:Sepsis D013601:T-Lymphocytes D050052:TRPC Cation Channels D019284:Thapsigargin D010738:Type C Phospholipases
Calcium-sensing receptor Lymphocytes Sepsis Cytokine Transient receptor potential channel