Cellular Electrophysiology

Abstract

The beginning of the era of cardiac electrophysiology can be dated to the end of the 19th century, when Einthoven discovered the ECG and described its configuration [1], more quantitatively defined in a later study [2]. While the ECG remains an essential clinical tool and a symbol of cardiac electrophysiology, the discipline has evolved to address the function of single myocytes, or even of specific processes within myocytes. Myocytes represent the functional unit of cardiac muscle; nonetheless, the heart behaves more or less like an electrical syncytium, whose global activity depends on low resistance coupling between the myocytes. The phrase “more or less” is used here intentionally to imply that, while the activity intrinsic to individual myocytes is affected by coupling, its features remain recognizable within the context of the whole heart and are important to determine its function. The ECG signal represents the electrical activity of the whole organ and its relation with the activity of individual myocytes is quite complex. Indeed, the potentials recorded by body surface electrodes are affected by spatial and temporal summation of myocyte activity at different locations in the heart. This results in so much cancellation of electrical signals, especially during the repolarization phase [3], that the same ECG pattern may be compatible with different activation and repolarization sequences. This implies that it would be theoretically possible to construct the ECG from the action potentials of all underlying myocytes, but we cannot deduce individual myocyte behaviour from the ECG, a condition recognized by biophysicists as the ‘inverse problem’ [4]. In the same way, analysis of the mechanisms and modulation of the electrical activity of single myocytes provides information relevant to whole heart function, which could not be obtained from the ECG. This chapter will deal with the basic mechanisms of myocyte functions such as excitation, repolarization and automaticity, which are relevant to the initiation and orderly propagation of electrical activity in the whole heart. The aim is to provide a link between phenomena at the molecular level, potential targets of drugs therapy or genetic manipulation, and macroscopic electrical behaviour. We have focused on issues essential to pursue this aim, sacrificing to clarity some of the overwhelming complexity of cardiac cell physiology. Reviews have been quoted to cover settled topics, reserving reference to original papers to more recent or controversial issues.