Multiple studies have demonstrated that the normal function and morphology of cardiac TCs are severely disrupted during myocardial infarction [45,49,50]. At first glance, this finding is not very surprising, given that the myocardial ischemia, with subsequent apoptosis, necrosis, and overall derangement of the cellular microenvironment, alters all the cell populations in the affected site, including TCs. It would suggest that the loss of TCs is merely a consequence of pathological processes occurring in the infarcted myocardium. It is indeed the case, but it has to be stated that previous studies found out that TCs are particularly fragile during hypoxia; hence, they are perhaps among the first cell populations negatively affected by the lack of nutrients and oxygen, leading to further derangement of normal TC-dependent myocardial architecture and function [45]. The most dreaded consequence of myocardial infarction in those patients who survive is the loss of contractile tissue, which is replaced by functionally inferior connective tissue scar, resulting in the loss of inotropic capacity of the heart, eventually progressing to heart failure [51]. The current research shows that TCs may also play a role in the development of these deleterious outcomes, not only in the pathogenesis of the myocardial infarction itself. This is documented by the experimental data, which indicate that TCs can be negatively influenced by dynamical changes in the composition of the extracellular matrix during the reparation process [52]. Moreover, according to a study of TCs and their involvement in the pathogenesis of fibrotic remodeling of the colonic wall in ulcerative colitis, it has been hypothesized that the loss of TCs may lead to deregulation of fibroblast to myofibroblast transition [53]. This transition also promotes cardiac fibrosis since myofibroblasts are excessively active in the synthesis of the extracellular matrix components [54]. The loss of TCs was also described in myocardial fibrotic lesions in patients diagnosed with systemic sclerosis, underscoring the importance of TCs in normal tissue maintenance [55].

Arrhythmias of different etiologies have also been discussed in relation to the possible role of TCs in their development. It is not at all surprising, given that TC discovery is closely linked to ICCs—pacemaker cells of the gut. TCs, formerly known as ICLCs, have been previously described in various organs participating in electrophysiological processes, including mechanoelectrical transduction and pacemaking [56]. DeSimone et al. found out that myocardial TCs of a dog express anoctamin-1. This voltage-gated calcium-activated anion channel is also found in ICCs as a major ion channel responsible for their pacemaker function. These results suggest that electrophysiological regulation and, thus, potential significance in arrhythmogenesis could be linked to myocardial TCs [57]. Not only that, Mitrofanova et al. also described TCs in the human sinoatrial node in close vicinity to pacemaker cells and contractile cardiac muscle cells using immunohistochemistry, confocal laser scanning microscopy, and TEM. The authors hypothesized about the modulating effects of TCs, although conclusive knowledge on their precise role has not been obtained. Future research may elucidate the role of TCs in the regulation of cardiac electrophysiology in the sinoatrial node—the top tier of normal heart rhythm [58]. Back in 2008, when TCs were known only for about 3 years and still referred to as ICLCs, Gherghiceanu et al. demonstrated the presence of TCs in the myocardial sleeves of the human pulmonary veins. According to their immunohistochemical and ultrastructural analysis of TCs in this location, the authors assumed that TCs may act as yet unrecognized agents in the pathogenesis of atrial fibrillation. This assumption was made according to the observation of the TC-derived 3D interstitial network among different components of the myocardial sleeve, including blood vessels, nerves, and cardiomyocytes. Since it is known that the myocardial sleeves can be a source of ectopic beats which can initiate the atrial fibrillation, the authors pondered on the possibility of implicating TCs in this pathological condition [59].