Aim Altered organization of the transverse‐tubular network is an early pathological event occurring even prior to the onset of heart failure. Such t‐tubular remodelling disturbs the synchrony and signalling between membranous and intracellular ion channels, exchangers, receptors and ATPases essential in the dynamics of excitation‐contraction coupling, leading to ionic abnormality and mechanical dysfunction in heart disease progression. In this study, we investigated whether a disrupted t‐tubular network has a direct effect on cardiac mechano‐energetics. Our aim was to understand the fundamental link between t‐tubular remodelling and impaired energy metabolism, both of which are characteristics of heart failure. We thus studied healthy tissue preparations in which cellular processes are not altered by any disease event. Methods We exploited the “formamide‐detubulation” technique to acutely disrupt the t‐tubular network in rat left‐ventricular trabeculae. We assessed the energy utilization by cellular Ca2+ cycling and by crossbridge cycling, and quantified the change of energy efficiency following detubulation. For these measurements, trabeculae were mounted in a microcalorimeter where force and heat output were simultaneously measured. Results Following structural disorganization from detubulation, muscle heat output associated with Ca2+ cycling was reduced, indicating impaired intracellular Ca2+ homeostasis. This led to reduced force production and heat output by crossbridge cycling. The reduction in force‐length work was not paralleled by proportionate reduction in the heat output and, as such, energy efficiency was reduced. Conclusions These results reveal the direct energetic consequences of disrupted t‐tubular network, linking the energy disturbance and the t‐tubular remodelling typically observed in heart failure.

Networks of neurons are typically studied in the field of Criticality. However, the study of astrocyte networks in the brain has been recently lauded to be of equal importance to that of the neural networks. To date criticality assessments have only been performed on networks astrocytes from healthy rats, and astrocytes from cultured dissociated resections of intractable epilepsy. This work, for the first time, presents studies of the critical dynamics and shape collapse of calcium waves observed in cultures of healthy human astrocyte networks in vitro, derived from the human hNT cell line. In this article, we demonstrate that avalanches of spontaneous calcium waves display strong critical dynamics, including power-laws in both the size and duration distributions. In addition, the temporal profiles of avalanches displayed self-similarity, leading to shape collapse of the temporal profiles. These findings are significant as they suggest that cultured networks of healthy human hNT astrocytes self-organize to a critical point, implying that healthy astrocytic networks operate at a critical point to process and transmit information. Furthermore, this work can serve as a point of reference to which other astrocyte criticality studies can be compared.