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. Author manuscript; available in PMC: 2014 Mar 26.

Published in final edited form as: Compr Physiol. 2013 Apr;3(2):667–692. doi: 10.1002/cphy.c110014

Effects of inducible heart-specific ClC-3 knockout on cardiac volume-regulated Cl⁻ current (VRCC) and heart function. (A) Representative current traces in isotonic condition and under hypotonic challenge recorded in freshly isolated atrial myocytes from the inducible heart-specific ClC-3 knockout (doxyhsClC-3^−/−) mice with doxycycline (on Doxy) in the diet (panel a), or after withdraw of doxycycline (off Doxy) from the diet for 3 weeks (panel b). (c) Summary of VRCC current densities in isotonic and hypotonic solutions, recorded at +80 mV and −80 mV. (B) Representative M-mode echocardiography from on Doxy (a) and off Doxy (b) mice. (C) Time-dependent changes in M-mode echocardiogram of age matched on Doxy or off Doxy for 1.5 and 3 weeks. *, P < 0.05; **, P < 0.01; ***, P < 0.001 versus off Doxy 0 week;^#, P < 0.05;^##, P < 0.01;^###, P < 0.001 versus on Doxy at the same time point. (D) Comparison of hearts isolated from age-matched (11-week old) doxyhsClcn3^−/− mice on Doxy or off Doxy for 3 weeks. Hearts were cleaned up blood and connective tissues and fixed in 4% paraformaldehyde. [Adapted, with permission, from Xiong et al. (168).]

Effects of inducible heart-specific ClC-3 knockout on cardiac volume-regulated Cl⁻ current (VRCC) and heart function. (A) Representative current traces in isotonic condition and under hypotonic challenge recorded in freshly isolated atrial myocytes from the inducible heart-specific ClC-3 knockout (doxyhsClC-3^−/−) mice with doxycycline (on Doxy) in the diet (panel a), or after withdraw of doxycycline (off Doxy) from the diet for 3 weeks (panel b). (c) Summary of VRCC current densities in isotonic and hypotonic solutions, recorded at +80 mV and −80 mV. (B) Representative M-mode echocardiography from on Doxy (a) and off Doxy (b) mice. (C) Time-dependent changes in M-mode echocardiogram of age matched on Doxy or off Doxy for 1.5 and 3 weeks. *, P < 0.05; **, P < 0.01; ***, P < 0.001 versus off Doxy 0 week;^#, P < 0.05;^##, P < 0.01;^###, P < 0.001 versus on Doxy at the same time point. (D) Comparison of hearts isolated from age-matched (11-week old) doxyhsClcn3^−/− mice on Doxy or off Doxy for 3 weeks. Hearts were cleaned up blood and connective tissues and fixed in 4% paraformaldehyde. [Adapted, with permission, from Xiong et al. (168).]