مقاله انگلیسی رایگان در مورد کم و زیاد بودن کلسیم در قلب – وایلی ۲۰۱۷

It is well-established that contraction of the heart is controlled by changes of cytoplasmic calcium concentration ([Ca2+]i). [Ca2+]i must be high enough in systole to activate the contractile proteins in order to pump blood out of the heart. Equally importantly, it must fall during diastole to low enough levels that the muscle of the heart relaxes so that the chambers can refill with blood. The aim of this article is to discuss factors responsible for both the rise and fall of [Ca2+]i . The importance of calcium in contraction of the heart was originally demonstrated by Sydney Ringer (Ringer, 1883). I have recently described both the serendipitous nature of his discovery and the manner in which it was published (Eisner, 2014). In the subsequent 130 years it has become clear that changes of intracellular calcium concentration ([Ca2+]i) regulate the function of virtually all organs. It took, however, almost one hundred years after Ringer’s discovery to measure directly the transient elevation of [Ca2+]i (the calcium transient) which underlies cardiac contraction (Allen & Blinks, 1978; Allen & Kurihara, 1980). Calcium versus other signalling modalities. Calcium has its actions by binding to proteins and thereby changing their shape and properties (Fig. 1A). In the case of striated muscle, calcium binds to troponin and the resulting movement of tropomyosin allows actin and myosin to interact. There are, of course, many other ways to alter the properties of proteins including phosphorylation and nitrosylation. This immediately raises the question of what are the advantages and disadvantages of using calcium as opposed to other ways of modifying protein structure? One great advantage of calcium is its speed of action. [Ca2+]i rises and Ca2+ ions bind to troponin very quickly and. In cardiac muscle contraction can be 50% complete within 200 ms (Fig 1A). In contrast regulation by phosphorylation is much slower. Fig 1B shows the effects of beta adrenergic stimulation on the Ca current. This takes about 20 s to be 50% complete (Frace et al., 1993). This slower timescale is due to the many steps involved; agonist binding to the receptor, generation of cyclic AMP, and, finally, the activation of protein kinase A which then phosphorylates the L-type channel. Although signalling by phosphorylation is slower than that by Ca2+, it has the advantage that it can be regulated in a much more subtle way. Specific phosphodiesterases can break down cAMP and various regulators affect the activities of the kinases and phosphatases. Another significant advantage of control by phosphorylation is that it can be reversed simply by dephoshorylation. In contrast, Ca2+ ions cannot be destroyed. The only way to reverse Ca2+ binding is to pump the Ca2+ across a membrane either out of the cell or into an intracellular store. Put simply, Ca2+ must be recycled and many of the results and conclusions of the remainder of this review follow from this.