ABSTRACT
The heart is a powerful pump that enables the circulation of oxygen and nutrients to every single cell of the organism via the blood vessels. It is composed of four chambers, and communication between them is rhythmically regulated to ensure an efšcient and regular exchange of blood throughout the body. This rhythmic activity is controlled by electrical signals evoked by spontaneously electrically active cells, referred to as pacemaker cells, and transmitted to muscle cells that in turn contract in a synchronous manner. When the electrical signal reaches a muscle cell, it induces a depolarization at the cell membrane level, driven by the opening of sodium channels that are responsible for the rapid upstroke of the resultant action potential (AP), and this ultimately leads to the opening of L-type voltage-gated calcium channels (L-VGCC). This allows the in·ux of calcium into the cytosol of the cell, which in turn can activate calcium release channels (ryanodine receptors or RyR type 2) localized on the membrane of intracellular stores, i.e., the sarcoplasmic reticulum (SR). RyRs are huge macromolecular complexes that allow for the massive and rapid release of calcium ions from the SR into the cytosol (millions of ions per second). This important mechanism of calcium signaling amplišcation between L-VGCC and RyR has been termed calcium-induced calcium release. The resulting increase of intracellular calcium concentration leads eventually to the shortening of muscle cells (i.e., contraction) by a calcium-dependent conformational change of the proteins constituting the myošlaments. This phenomenon is known as excitation-contraction coupling (or ECC; Figure 22.1). The termination of this process occurs by reuptake into the SR and mitochondria (by the sarco/endoplasmic reticulum calcium ATPase [SERCA] pump and by the mitochondrial calcium uniporter, respectively) and extrusion (ef·ux through the plasma membrane calcium ATPase and by the sodium/calcium exchanger) of calcium. Hence muscle relaxation can take place.
