T-Tubular Electrical Defects Contribute to Blunted β-Adrenergic Response in Heart Failure
AbstractAlterations of the β-adrenergic signalling, structural remodelling, and electrical failure of T-tubules are hallmarks of heart failure (HF). Here, we assess the effect of β-adrenoceptor activation on local Ca2+ release in electrically coupled and uncoupled T-tubules in ventricular myocytes from HF rats. We employ an ultrafast random access multi-photon (RAMP) microscope to simultaneously record action potentials and Ca2+ transients from multiple T-tubules in ventricular cardiomyocytes from a HF rat model of coronary ligation compared to sham-operated rats as a control. We confirmed that β-adrenergic stimulation increases the frequency of Ca2+ sparks, reduces Ca2+ transient variability, and hastens the decay of Ca2+ transients: all these effects are similarly exerted by β-adrenergic stimulation in control and HF cardiomyocytes. Conversely, β-adrenergic stimulation in HF cells accelerates a Ca2+ rise exclusively in the proximity of T-tubules that regularly conduct the action potential. The delayed Ca2+ rise found at T-tubules that fail to conduct the action potential is instead not affected by β-adrenergic signalling. Taken together, these findings indicate that HF cells globally respond to β-adrenergic stimulation, except at T-tubules that fail to conduct action potentials, where the blunted effect of the β-adrenergic signalling may be directly caused by the lack of electrical activity. View Full-Text
Share & Cite This Article
Crocini, C.; Coppini, R.; Ferrantini, C.; Yan, P.; Loew, L.M.; Poggesi, C.; Cerbai, E.; Pavone, F.S.; Sacconi, L. T-Tubular Electrical Defects Contribute to Blunted β-Adrenergic Response in Heart Failure. Int. J. Mol. Sci. 2016, 17, 1471.
Crocini C, Coppini R, Ferrantini C, Yan P, Loew LM, Poggesi C, Cerbai E, Pavone FS, Sacconi L. T-Tubular Electrical Defects Contribute to Blunted β-Adrenergic Response in Heart Failure. International Journal of Molecular Sciences. 2016; 17(9):1471.Chicago/Turabian Style
Crocini, Claudia; Coppini, Raffaele; Ferrantini, Cecilia; Yan, Ping; Loew, Leslie M.; Poggesi, Corrado; Cerbai, Elisabetta; Pavone, Francesco S.; Sacconi, Leonardo. 2016. "T-Tubular Electrical Defects Contribute to Blunted β-Adrenergic Response in Heart Failure." Int. J. Mol. Sci. 17, no. 9: 1471.
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.