Abstract 14601: TRPC1 Channel Is Upregulated in Atria of Patients With Atrial Fibrillation
Introduction: Our previous study demonstrated that the non-selective cation current mediated by TRPC1 channels is present in human atrial myocytes and activated by endothelian-1 (ET-1).
Hypothesis: Regulation of TRPC1 channels by ET-1 is related to activation of intracellular molecular signals and TRPC1 channels are upregulated in atria of patients with persistent atrial fibrillation (AF).
Methods: A whole-patch voltage-clamp technique and molecular biological approaches were used to record TRPC1 current and to determine the related gene and protein expression in atrial myocytes and/or tissue specimens of sinus rhythm (SR, n=35) or AF (n=30) patients who underwent cardiac surgery.
Results: It was found that ET-1 activated TRPC1 current more in AF myocytes than in SR myocytes (n=10, P<0.05 vs. control). ET-1-evoked TRPC1 current was inhibited by both ETA and ETB receptor antagonists BQ-123 and BQ788 or protein kinase C (PKC) inhibitor chelerythrine. ETA receptor-mediated TRPC1 channel activity was selectively inhibited by phosphoinositol-3-kinase (PI3K) inhibitors wortmannin, while ETB receptor-mediated TRPC1 channel activity was inhibited by the phospholipase C (PLC) inhibitor U73122. Real-time PCR and Western blot analysis revealed that mRNA and protein levels of TRPC1 and ETA receptor, but not ETB receptor, were significantly increased in human atrial specimens from AF patients.
Conclusion: Our results demonstrate for the first time that TRPC1 and ETA receptor are upregulated in atria of AF patients. Increase of TRPC1 current by ET-1 is likely involved in atrial electrical remodelingin AF patients via activating PKC through the distinct phospholipids pathways PI3K and PLC.
Author Disclosures: K. Zhang: None. F. Qiu: None. Q. Yang: None. G. Xiao: None. G. Li: None. Y. Wang: None.
- © 2016 by American Heart Association, Inc.