BBB seminar: Ole M. Sejersted
Heart failure is closely linked to deranged ultrastructure of cardiac myocytes
Ole M. Sejersted
Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo
Heart failure, especially systolic heart failure, is characterized by weak and slow contractions of the heart. Since power is the product of force and velocity, reduction of both contribute to poor performance of the failing heart. Weak contractions are linked to reduced release of intracellular calcium. The available amount of releasable calcium and the trigger for release are highly dependent on electrical events (membrane and action potential). On the other hand, slow contractions seem to be caused by dyssynchronous release of calcium inside the cardiac myocytes. The focus of the talk will be on the ultrastructural elements and membrane proteins that maintain rapid and synchronous calcium release at the cellular level. Contraction of the cardiac myocytes is elicited by the action potential travelling to the cell interior by way of the t-tubular system. T-tubules are extensive invaginations of the cell membrane forming a regular striated pattern of transverse tubules located at the Z-lines. Here they form dyads that are points of close contact with the sarcoplasmic reticulum (SR) that contains the calcium to be released. The depolarization will cause the L-type calcium channels to open and the calcium that enters the dyadic cleft will bind to the calcium release channels (ryanodine receptors) of the SR so that they open. This calcium-induced calcium release gives rise to a calcium transient that is highly synchronous throughout the cell. In heart failure spontaneous calcium release can occur giving rise to arrhythmogenic calcium waves. Also, the t-tubules are disrupted in heart failure, causing dyssynchronous cellular calcium release. Intact ultrastructure and precise localization of calcium handling proteins are required for normal cardiac function.
Chairperson: Rolf K. Reed, Department of Biomedicine