The structure and function of cardiac t-tubules in health and disease

Abstract

The transverse tubules (t-tubules) are invaginations of the cell membrane rich in several ion channels and other proteins devoted to the critical task of excitation-contraction coupling in cardiac muscle cells (cardiomyocytes). They are thought to promote the synchronous activation of the whole depth of the cell despite the fact that the signal to contract is relayed across the external membrane. However, recent work has shown that t-tubule structure and function are complex and tightly regulated in healthy cardiomyocytes. In this review, we outline the rapidly accumulating knowledge of its novel roles and discuss the emerging evidence of t-tubule dysfunction in cardiac disease, especially heart failure. Controversy surrounds the t-tubules' regulatory elements, and we draw attention to work that is defining these elements from the genetic and the physiological levels. More generally, this field illustrates the challenges in the dissection of the complex relationship between cellular structure and function.

Integrin-linked kinase mediates force transduction in cardiomyocytes by modulating SERCA2a/PLN function

“…SERCA2a is located in the sarcoplasmic reticulum (SR) that comprises the main calcium release units that are concentrated at Z lines 16 . Confocal microscopy in human myocardial samples from patients with TF revealed Z-disk colocalization of endogenous ILK with SERCA-2a and PLN and the Z-disk protein a-actinin, whereas there was no spatial overlap detectable of ILK or SERCA2a with the sacromeric protein Troponin T (Fig.…”

Ectopic expression of Cdk8 induces eccentric hypertrophy and heart failure

“…A reduced or disorganized T-tubule network is common in rodent models of heart disease and in human hearts from patients with HCM, DCM, and ischemic HF (reviewed in ref. 48). As T-tubules are critical for efficient Ca 2+ -induced Ca 2+ release responsible for excitation-contraction coupling, the abnormal Ca 2+ dynamics we found for Tg8a hearts may be due to the primary defects in T-tubule formation.…”

Heart Failure with Preserved Ejection Fraction

“…T-tubule disorganization has also been demonstrated in various human studies and animal models [58][59][60]. Recent evidence suggests that t-tubules might have a significant role in Ca 2+ extrusion from the cell, however, the exact role of t-tubule dysfunction in HFpEF requires further studies [61][62][63].…”