2018
DOI: 10.3389/fphys.2018.01302
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Partial Mechanical Unloading of the Heart Disrupts L-Type Calcium Channel and Beta-Adrenoceptor Signaling Microdomains

Abstract: Introduction: We investigated the effect of partial mechanical unloading (PMU) of the heart on the physiology of calcium and beta-adrenoceptor-cAMP (βAR-cAMP) microdomains. Previous studies have investigated PMU using a model of heterotopic-heart and lung transplantation (HTHAL). These studies have demonstrated that PMU disrupts the structure of cardiomyocytes and calcium handling. We sought to understand these processes by studying L-Type Calcium Channel (LTCC) activity and sub-type-specific βAR-cAMP signalin… Show more

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Cited by 9 publications
(8 citation statements)
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“…This may be caused by a global reduction in phosphorylation levels, as it has been suggested to happen in LVADsupported hearts [9]. The way LVAD implantation reduces the Po of the channels could be a passive process, as it has been shown previously that unloading a healthy heart also reduces the Po of LTCC [32]. Furthermore, we demonstrate that LVAD implantation is associated with a reduction in arrhythmogenic propensity, as blockade of CaM-KII and PKA in the simulations resulted in suppression of the EADs in HF cells (Fig.…”
Section: Pro-arrhythmic Ltccs Can Be Attenuated By Lvad Implantationmentioning
confidence: 92%
“…This may be caused by a global reduction in phosphorylation levels, as it has been suggested to happen in LVADsupported hearts [9]. The way LVAD implantation reduces the Po of the channels could be a passive process, as it has been shown previously that unloading a healthy heart also reduces the Po of LTCC [32]. Furthermore, we demonstrate that LVAD implantation is associated with a reduction in arrhythmogenic propensity, as blockade of CaM-KII and PKA in the simulations resulted in suppression of the EADs in HF cells (Fig.…”
Section: Pro-arrhythmic Ltccs Can Be Attenuated By Lvad Implantationmentioning
confidence: 92%
“…Pathological de-tubulation can be elicited by atrophy as well as hypertrophy in the context of failure or even changes in myocardial provenance. In these experiments, it was demonstrated that de-tubulation resulted in ‘gain-of-function’ with respect to βAR-cAMP, but calcium channel function was down-regulated in the case of atrophy [ 114 ]. The electrophysiological outcome of this scenario in the wider heart is therefore unclear.…”
Section: Experimental Techniques To Probe Tat/βar Effects In Cardiomyocytes With ‘Tubular’ Resolutionmentioning
confidence: 99%
“…This effect was attributed to TAT system dysregulation, resulting in an increased frequency and altered morphology of Ca 2+ sparks [42]. Further studies have indicated that PMU significantly reduced the β2AR-induced cAMP response in the cytosolic, but not RII-PKA compartment [52]. TAT configuration is therefore dynamically tuned to a changing microenvironment rather than a static property of a specific physiological state.…”
Section: Pathologymentioning
confidence: 99%