Does the 'coupled clock' make the heart tick?

Abstract

This editorial refers to ‘Cardiac ryanodine receptors control heart rate and rhythmicity in adult mice’, by M. J. Bround et al ., pp. 372–380, this issue. The first written descriptions of the regular beating pattern of the heart (as measured by pulse) are found in the often fragmentary writings of the ancient Greek physicians and scientists.1 However, it was not until 1943 that the electrical events associated with the initiation of the cardiac impulse were first recorded in the vertebrate heart.2 Using extracellular electrodes, Emil Bozler reported that a local, slowly rising wave of negativity proceeded each impulse (extracellular action potential) in the sinus venosus of the turtle heart and in right atrial tissue prepared from a variety of mammalian species (rabbit, dog, and cat).2 He further demonstrated that this spontaneous activity was depressed by the application of acetylcholine. He used the term ‘pacemaker prepotential’ to describe these changes in membrane potential that led to cardiac action potentials. Interestingly, in the same paper, he also was the first to recognize that oscillations in membrane potential that occurred following an action potential (afterdepolarizations) could induce extra impulses. He concluded that ‘It is apparent that many rhythmic phenomena in cardiac muscle cannot be understood if only conducted impulses are recorded. It is quite possible, therefore, that local, graded activity which may take place in the ‘resting’ state offers the key to understanding of a variety of disturbances of the rhythmicity of the heart.’2 It has been nearly 70 years since this seminal study and yet the ionic/molecular basis of the cardiac pacemaker has not been …