A small leak may sink a great ship but what does it do to the heart?

摘要

While Benjamin Franklin realized the importance of a leak, in much of cell physiology the term 'leak' has been used to describe the unmeasurable. In the original formulation for the squid giant axon, the leak included all ionic movements not through voltage gated sodium and potassium channels (Hodgkin & Huxley, 1952). In other words it represented everything which was not characterized in a more sophisticated way. More recent work has shown for a variety of biological membranes that leaks are often made up from the activity of many ion channels. It is now well established that most of the Ca~(2+) that activates contraction in the heart is provided by release from the sarcoplasmic reticulum (SR). Ca~(2+) is released through a specialized channel known as the ryanodine receptor (RyR). The RyRhas the important property that the probability that it is open (po) is increased by an increase of cyto-plasmic Ca~(2+) concentration ([Ca~(2+)]i).