238 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION I 



of the contractile tension of a whole frog ventricle 

 and the transmembrane action potential from a 

 single ventricular cell. It can be seen that the up- 

 stroke of the action potential precedes contraction 

 and the downstroke precedes relaxation. Since the 

 onset and duration of the action potential are about 

 the same in all ventricular cells, it appears that this 

 relation between electrical activity and contraction 

 exists throughout the myocardium. 



In relation to contractile activity, a survey of 

 cardiac electrophysiology must deal comprehensively 

 with the following questions, a) What mechanisms 

 lead to the rhythmic contraction of the heart and 

 how are these affected by the regulatory innervation? 



b) What factors determine the length of systole and 

 diastole, and how do they vary with rate? Ancillary 

 to this question is the problem of how changes in the 

 membrane potential control contractile activity. 



c) Since cardiac cells are anatomically distinct and 

 do not receive motor innervation, how is effectively 

 synchronous contraction of all the cells achieved? 



The first two questions are concerned with the 

 temporal aspects of the control of cardiac contraction 

 and hence with the membrane electrical properties 

 of individual cells throughout the heart. The third 

 question concerns the spatial aspects of the control 

 of contraction, i.e., the mechanism whereby activity 



14 SECONDS 



FIG. I . Cellular transmembrane potential and contractile 

 tension of isolated, perfused frog ventricle. Abscissa : time. 

 Ordinates ; upper trace, potential inside cell minus potential 

 outside (£) in millivolts; lower trace, contractile tension (T) 

 in arbitrary (linear) units. Note the delay between the up- 

 stroke of the action potential and the beginning of contrac- 

 tion; and between fast repolarization and the beginning of 

 relaxation. The time of occurrence of the action potential 

 upstroke varies by perhaps as much as 0.2 sec from cell to cell 

 in the intact heart, but the variation is much less in this record 

 because the cells were excited nearly simultaneously by a 

 current pulse. (Lee & Woodbury, unpublished data.) 



in one cell initiates activity in neighboring cells. 

 Knowledge of the temporal and spatial aspects of 

 cardiac electrical activity and the laws describing 

 the flow of curreitt in a volume conductor with 

 known characteristics is the necessary and sufficient 

 physical basis for understanding the electrocardio- 

 gram. 



Except for the extraordinarily long duration of 

 the action potential, the electrical and excitable 

 properties of cardiac muscle are similar to those of 

 unmyelinated nerve and skeletal muscle. Most of 

 our detailed knowledge of the properties of excitable 

 membranes comes from Hodgkin and Huxley's 

 analysis and synthesis of voltage clamp records from 

 squid giant axons (53, 60). Knowledge of cardiac 

 membrane properties is based on more indirect 

 experiments that have been interpreted in the light 

 of the behavior of the squid axon. Analysis in cardiac 

 electrophysiology therefore requires knowledge of 

 the corresponding changes in nerve. The aspects of 

 nerve and cardiac electrophysiology to be considered 

 in this chapter are: a) the maintenance of steady 

 ionic and potential gradients across the cell membrane 

 by active ion transport; /') the passive electrical 

 properties of cells; c) the ionic conductance changes 

 which are responsible for the excitable, all-or- 

 nothing properties of the membrane; and d) the 

 mechanism of impulse propagation from cell to cell, 

 unique to cardiac and visceral smooth muscle. 



The interpretation of the electrophysiology of 

 cardiac cells given here is based on Hodgkin and 

 Huxley's membrane ionic theory (cf. 53). This theory, 

 although not universally accepted [it is sometimes 

 termed a hypothesis (112)], is so useful in the syn- 

 thesis and interpretation of such a wide range of 

 experimental results that there is little doubt of its 

 over-all \alidity. Since Tasaki's chapter on the 

 ''Conduction of the Nerve Impulse" (112) contains 

 only a brief mention of this theory, it must be pre- 

 sented here so that the events in cardiac cells can be 

 discussed coherently. Hodgkin's reviews (52, 53) and 

 the original papers by Hodgkin & Huxley, and their 

 colleagues (57-65) should be consulted for detailed 

 descriptions of the ionic theory and references to the 

 pertinent literature. A somewhat condensed and 

 simplified treatment of the ionic theory appears in a 

 recent textbook (135, 138). The history of electro- 

 physiology has been covered adequately in the 

 chapters by Brazier (5) and Tasaki (112); additional 

 details on the history and current knowledge of 

 cardiac electrophysiology appear in the monographs 

 of Weidmann (129, in German) and Hoffman & 



