Streptomycin and its analogues are potent inhibitors of the hypotonicity‐induced Ca2+ entry and Cl− channel activity

FEBS Letters

Chiu, Wen-Tai¹  Shen, Meng-Ru²  Chou, Cheng-Yang³ 

[1] Department of Physiology, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan;Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan;Department of Obstetrics and Gynecology, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan

关键词: Streptomycin;    Volume regulation;    Cervical cancer cell;    RVD;    regulatory volume decrease;    [Ca2+]i;    cytosolic Ca2+;   

DOI  :  10.1016/S0014-5793(03)01231-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Streptomycin is a common antibiotic used in culture media. It is also a known blocker of stretch-activated and mechanosensitive ion channels in neurons and cardiac myocytes. But very little information is available on its effect in the regulation of epithelial ion channels. Osmotic swelling is a kind of mechanical stretch. The opening of stretch-activated Ca²⁺ channels contributes to hypotonicity-induced Ca²⁺ influx which is necessary for the activation of volume-regulated Cl⁻ channels in human cervical cancer cells. This study aimed to investigate the role of streptomycin in cell volume regulation. Treatment of cervical cancer SiHa cells with streptomycin and its analogues (gentamicin and netilmicin) did not affect the basal cytosolic Ca²⁺ ([Ca²⁺]_i) level. But it attenuated the hypotonicity-stimulated increase of [Ca²⁺]_i in a dose-dependent manner with half-maximal inhibitory concentrations (IC₅₀) of 25, 90 and 200 μM for streptomycin, gentamicin and netilmicin, respectively, when measured at room temperature. In contrast, under free extracellular Ca²⁺ condition, hypotonic stress only induced a small, progressive increase of [Ca²⁺]_i, while 500 μM streptomycin did not affect this Ca²⁺ signaling. Streptomycin and its analogues (gentamicin and netilmicin) also inhibited the activation of volume-regulated Cl⁻ channels in a dose-dependent manner with IC₅₀ of 30, 95 and 250 μM at room temperature, respectively. Chronic culture with 50 μM streptomycin downregulates the activity of volume-regulated Cl⁻ channels and retards the process of regulatory volume decrease in SiHa cells and MDCK cells. We suggest that using cells chronically cultured with streptomycin to study epithelial ion channels risks studying cellular and molecular pathology rather than physiology.

【 授权许可】

Unknown