Caveolin 3-dependent loss of t-tubular ICa during hypertrophy and heart failure in mice

Experimental Physiology
Simon BryantC H Orchard

Abstract

What is the central question of this study? Heart failure is associated with redistribution of L-type Ca2+ current (ICa ) away from the t-tubule membrane to the surface membrane of cardiac ventricular myocytes. However, the underlying mechanism and its dependence on severity of pathology (hypertrophy versus failure) are unclear. What is the main finding and its importance? Increasing severity of response to transverse aortic constriction, from hypertrophy to failure, was accompanied by graded loss of t-tubular ICa and loss of regulation of ICa by caveolin 3. Thus, the pathological loss of t-tubular ICa , which contributes to impaired excitation-contraction coupling and thereby cardiac function in vivo, appears to be attributable to loss of caveolin 3-dependent stimulation of t-tubular ICa . Previous work has shown redistribution of L-type Ca2+ current (ICa ) from the t-tubules to the surface membrane of rat ventricular myocytes after myocardial infarction. However, whether this occurs in all species and in response to other insults, the relationship of this redistribution to the severity of the pathology, and the underlying mechanism, are unknown. We have therefore investigated the response of mouse hearts and myocytes to press...Continue Reading

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Citations

Jul 22, 2018·American Journal of Physiology. Heart and Circulatory Physiology·Simon M BryantClive H Orchard
Feb 21, 2019·Experimental Physiology·Cherrie H T KongClive H Orchard
Jun 3, 2020·Journal of Cellular and Molecular Medicine·Jae Gyun OhDongtak Jeong
Feb 6, 2020·Biochemical Society Transactions·Cerrone R FosterHemal H Patel
Jan 24, 2020·Proceedings of the National Academy of Sciences of the United States of America·Ewan D FowlerMark B Cannell
Nov 27, 2018·Frontiers in Physiology·Ravi VaidyanathanLee L Eckhardt
Nov 25, 2020·International Journal of Molecular Sciences·Bhola Shankar Pradhan, Tomasz J Prószyński
Aug 17, 2021·Oxidative Medicine and Cellular Longevity·Rubin TanJie Cui

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Software Mentioned

MATLAB
pClamp
ImageJ

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