Ca2+ Signaling Triggered by Shear-Autocrine P2X Receptor Pathway in Rat Atrial Myocytes

Cellular Physiology and Biochemistry

Joon-Chul Kim¹ 

关键词: Shear stress;    AP-triggered Ca2+ wave;    Atrial myocytes;    ATP release;    P2X recceptor;   

DOI  :  10.1159/000495089

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Background/Aims The atrium is exposed to high shear stress during heart failure and valvular diseases. We aimed to understand atrial shear-induced Ca2+ signaling and its underlying mechanisms. Methods Pressurized micro-flow was applied to single rat atrial myocytes, and Ca2+ signal, membrane potential, and ATP release were assessed using confocal imaging, patch clamp technique, and luciferin-luciferase assay, respectively. Results Shear stress (∼16 dyn/cm2) induced global Ca2+ waves (∼0.1 events/s) from the periphery to the center of cells in a transverse direction (“T-wave”; ∼145 μm/s). Pharmacological interventions and simultaneous recording of membrane potential and Ca2+ demonstrated that shear-induced T-waves resulted from action potential (AP)-triggered Ca2+ release from the sarcoplasmic reticulum. T-waves were not sensitive to inhibitors of known shear signaling mechanisms except connexin hemichannels and ATP release. Shear stress caused ATP release from these myocytes (∼1.1x10-17 moles/unit membrane, µm2); ATP release was increased by enhancement of connexin hemichannels and suppressed by inhibition of the hemichannels, but not affected by inhibitors of other ATP release pathways. Blockade of P2X receptor, but not pannexin or the Na+-Ca2+ exchanger, eliminated shear-induced T-wave initiation. Conclusion Our data suggest that shear stress triggers APs and concomitant Ca2+ signaling via activation of P2X receptors by connexin hemichannel-mediated ATP release in atrial myocytes.

【 授权许可】

CC BY-NC-ND