Evolution of automaticity of heart pacemaker studied from a theoretical perspective

The pacemaker of the mammalian heart had developed a robust and yet a flexible system in the course of evolution whose function is based on multiple interactions at the sub-cellular, cellular and finally at the tissue level. These, in turn, should respond to extrinsic signals. Cardiac action potentials were explained for a long time based on the changes that occur at the cell surface. New hypothesis was put forward at the turn of the century that pointed to the role of intracellular calcium clock. Discovery of ryanodine receptors, fluorescence labeling techniques, confocal imaging and finally computer modeling of physiological processes had brought about a noticeable change that allowed development of a new concept of pacemaker automaticity. Reviewing all these developments we hereby put forward a few theoretical formulations that can turn out to be new instruments in advancing our knowledge of cardiac physiology. We had theorized that cardiac muscle is an emergent property of smooth muscle in the course of evolution, and that pacemaker activity of the cardiac muscle underwent a phase transition that finally led to the evolution of a structural pacemaker.