Calcium entry via TRPC1 channels activates chloride currents in human glioma cells

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• 作者：Vishnu Anand Cuddapah ; Kathryn L. Turner ; Harald Sontheimer ; ^{sontheimer@uab.edu}
• 关键词：Cl&minus ; channels ; TRP channels ; TRPC1 ; Glioma ; Glioblastoma ; Migration ; EGF ; ClC-3
• 刊名：Cell Calcium
• 出版年：2013
• 出版时间：March, 2013
• 年：2013
• 卷：53
• 期：3
• 页码：187-194
• 全文大小：1168 K

文摘

Malignant gliomas are highly invasive brain cancers that carry a dismal prognosis. Recent studies indicate that Cl^? channels facilitate glioma cell invasion by promoting hydrodynamic cell shape and volume changes. Here we asked how Cl^? channels are regulated in the context of migration. Using patch-clamp recordings we show Cl^? currents are activated by physiological increases of [Ca²⁺]_i to 65 and 180 nM. Cl^? currents appear to be mediated by ClC-3, a voltage-gated, CaMKII-regulated Cl^? channel highly expressed by glioma cells. ClC-3 channels colocalized with TRPC1 on caveolar lipid rafts on glioma cell processes. Using perforated-patch electrophysiological recordings, we demonstrate that inducible knockdown of TRPC1 expression with shRNA significantly inhibited glioma Cl^? currents in a Ca²⁺-dependent fashion, placing Cl^? channels under the regulation of Ca²⁺ entry via TRPC1. In chemotaxis assays epidermal growth factor (EGF)-induced invasion was inhibition by TRPC1 knockdown to the same extent as pharmacological block of Cl^? channels. Thus endogenous glioma Cl^? channels are regulated by TRPC1. Cl^? channels could be an important downstream target of TRPC1 in many other cells types, coupling elevations in [Ca²⁺]_i to the shape and volume changes associated with migrating cells.