Fra global til lokal - ny forståelse av den elektromekaniske koblingen i hjertet
Sammanfattning
Background. The coupling between depolarisation and contraction of cardiac myocytes is fundamental to the physiology and pathophysiology of the heart. This review describes how the coupling depends on the interaction between proteins in subcellular «microdomains».
Method. The review is based on the authors' own research and on a discretionary selection of articles found by means of a literature search in PubMed.
Results. Essential aspects of the physiology and pathophysiology of the heart must be understood in terms of the interaction between proteins in delimited parts of the cells. The significance of the binding protein ankyrin-B and the Ca2+ channel IP3R (inositol 1,4,5 triphosphate receptor) is best understood in this context. Abnormal function of ankyrin-B and IP3R is involved in congenital diseases with increased risk of arrhythmia and in weakened contractility and arrhythmias in connection with heart failure. The pathophysiological mechanism involves a change in Ca2+ homeostasis locally in the heart muscle cells.
Interpretation. Normal cardiac electromechanical coupling depends on control of ionic homeostasis in intracellular microdomains. Insight into the interaction between proteins in these «local neighbourhoods» provides new explanations for the pathophysiology of heart disease and paves the way for further research on arrhythmia mechanisms in hereditary diseases such as ankyrin-B syndrome.