2-APB and Capsazepine-induced Ca2+ Influx Stimulates Clathrin-dependent Endocytosis in Alveolar Epithelial Cells

Cellular Physiology and Biochemistry

关键词: Alveolar type II cells;    NCI-H441 cells;    2-APB;    Capsazepine;    Ca2+;    Endocytosis;   

DOI  :  10.1159/000272064

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Calcium as a second messenger influences many cellular and physiological processes. In lung, alveolar type II (ATII) cells sense mechanical stress and respond by Ca²⁺ dependent release of surfactant, which is essential for respiratory function. Nevertheless, Ca²⁺ signaling mechanisms in these cells - in particular Ca²⁺ entry pathways are still poorly understood. Herein, we investigated pharmacological properties of non-voltage-gated Ca²⁺ channel modulators in ATII and NCI-H441 cells and demonstrate that 2-Aminoethoxydiphenyl-borinate (2-APB) and capsazepine (CPZ) activate Ca²⁺ entry with pharmacologically distinguishable components. Surprisingly, 2-APB and CPZ activated clathrin dependent endocytosis in ATII and NCI-H441 cells, which was dependent on Ca²⁺ entry. The internalized material accumulated in non-acidic granules distinct from surfactant containing lamellar bodies (LB). LB exocytosis was not observed under these conditions. Our study demonstrates that 2-APB/CPZ induces Ca²⁺ entry which unlike ATP- or stretch-induced Ca²⁺ entry in ATII cells does not activate exocytosis but an opposing endocytotic mechanism.

【 授权许可】

CC BY-NC-ND