**7. Summary of the mechanisms for arrhythmia**

The three current mechanisms for arrhythmia assume that abnormalities in (a) the well-de‐ fined process of normal cardiac excitation-contraction coupling, (b) the propagation of elec‐ trical waves through the heart or (c) the electrical response of heart muscle to enormous faradic insults circumscribe all the properties of the myocardium needed to fully explain clinical arrhythmia including atrial fibrillation. In other words, all other non-electrical cell processes are by-standers in arrhythmogenesis and they little influence heart muscle electri‐ cal stability. None of these three theories is a true focal hypothesis for arrhythmia as envi‐ sioned by Engelman and championed by Scherf and others.

Our fourth view of arrhythmia proposes that non-electrical cell signaling events can destabi‐ lize the electrical activity of myocytes and conduction system cells. Such destabilization pro‐ duces isolated focal ectopic events or high frequency focal tachycardia or fibrillation. Thus our unconventional hypothesis for arrhythmia proposes that heart muscle can produce elec‐ tromechanical activity in two ways. First is by the well-defined pathway of sinus rhythm and impulse conduction. This pathway for normal heart electromechanical activity integra‐ tes heart function with systemic physiology. Second, the activation of a cellular 'arrhythmo‐ genic' signaling pathway can transform non-automatic myocytes into cells that spontaneously produce sporadic or high frequency electrical activity independent of exter‐ nal regulators like sinus rhythm or systemic physiology. Aberrant or exuberant myocyte or Purkinje cell voltage-independent calcium homeostasis is one means we have identified to activate this cryptic arrhythmogenic signaling pathway. The novel fourth mechanism out‐ lined below satisfies the requirements for a purely focal hypothesis for arrhythmia.
