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• W1510710257 abstract "This study investigated the function of FK506‐binding protein (FKBP12.6) using adenoviral‐mediated gene transfer to over‐express FKBP12.6 (Ad‐FKBP12.6) in adult rabbit ventricular cardiomyocytes. Infection with a β‐galactosidase‐expressing adenovirus (Ad‐LacZ) was used as a control. Peak‐systolic intracellular [Ca 2+ ] (measured with Fura‐2) was higher in the Ad‐FKBP12.6 group compared to Ad‐LacZ (1 Hz field stimulation at 37°C). The amplitude of caffeine‐induced Ca 2+ release was also greater, indicating a higher SR Ca 2+ content in the Ad‐FKBP12.6 group. Voltage clamp experiments indicated that FKBP12.6 over‐expression did not change L‐type Ca 2+ current amplitude or Ca 2+ efflux rates via the Na + –Ca 2+ exchanger. Ca 2+ transients comparable to those after Ad‐FKBP12.6 transfection could be obtained by enhancing SR Ca 2+ content of Ad‐LacZ infected cells with periods of high frequency stimulation. Line‐scan confocal microscopy (Fluo‐3 fluorescence) of intact cardiomyocytes stimulated at 0.5 Hz (20−21°C) revealed a higher degree of synchronicity of SR Ca 2+ release and fewer non‐responsive Ca 2+ release sites in the Ad‐FKBP12.6 group compared to control. Ca 2+ spark morphology was measured in β‐escin‐permeabilized cardiomyocytes at a free [Ca 2+ ] i of 150 n m . The average values of the spark parameters (amplitude, duration, width and frequency) were reduced in the Ad‐FKBP12.6 group. Increasing [Ca 2+ ] i to 400 n m caused coherent propagating Ca 2+ waves in the Ad‐FKBP12.6 group but only limited Ca 2+ release events were recorded in the control group. These data indicate that FKBP12.6 over‐expression enhances Ca 2+ transient amplitude predominately by increasing SR Ca 2+ content. Moreover, there is also evidence that FKBP12.6 can enhance the coupling between SR Ca 2+ release sites independently of SR content." @default.
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• W1510710257 date "2004-04-21" @default.
• W1510710257 modified "2023-10-11" @default.
• W1510710257 title "Over-expression of FK506-binding protein FKBP12.6 alters excitation-contraction coupling in adult rabbit cardiomyocytes" @default.
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• W1510710257 doi "https://doi.org/10.1113/jphysiol.2003.057166" @default.
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