CELLULAR ELECTROPHVSIOLOGY OF THE HEART 



279 



PASSIVE MEMBRANE PROPERTIES AND 

 INTERCELLULAR TRANSMISSION 



An adequate stimulus applied to any point in 

 cardiac tissue initiates an impulse which spreads 

 without decrement throughout the whole muscle. 

 Electrically, the tissue iaehaves like one large excitable 

 cell. Anatomically, the tissue is composed of discrete 

 cells, each bounded by a cell membrane (6, 91, 93, 

 94, 107, 108). If these cell membranes have a high 

 electrical resistance, as do those in other tissues, then 

 it is not clear how an active cell initiates activity in 

 its neighbors even though the cells are closely packed 

 (8-20 m/x spacing between membranes). The simplest 

 possibility is that activity spreads from cell to cell 

 by means of local currents as it does in single nerve 

 and skeletal muscle fibers. Another possibility is some 

 sort of synaptic transmission. In nerve and muscle 

 fibers, current flows from an inactive normally po- 

 larized region of membrane into an adjacent active 

 depolarized region via the extracellular fluid and 

 returns via the intracellular fluid. This flow even- 

 tually depolarizes the inacti\e membrane to threshold. 

 In turn, this portion of membrane becomes active 

 and serves as a source for adjacent inactive membrane. 

 If spread of activity in the heart is by local circuit 

 flow, some regions of the cell membrane must have a 

 comparatively low resistance to current flow, and 

 one of these regions must be closely approximated to a 

 like region of an adjacent cell. If these specialized 

 anatomical and functional requirements do not ob- 

 tain, intercellular transmission must be by other than 

 electrical means, e.g., chemical. 



A simple and fairly conclusive experiment helps to 

 distinguish between the two possible means of trans- 

 mission. If activity spreads by local circuit flow, a 

 current flowed through the membrane of one cell by 

 means of an intracellularly placed electrode must 

 appreciably affect the transmembrane potentials of 

 neighboring cells, i.e., the tissue would have elec- 

 trotonic properties. The absence of electrotonus from 

 cardiac tissue would establish that transmission is 

 not electrical. The presence of electrotonus would 

 not prove that transmission is electrical, but would 

 make this likely as the simplest hypothesis. A more 

 detailed consideration of electrotonic properties of 

 long, thin cells may be found in Tasaki's chapter 

 (112). The basic mathematical and experimental 

 analysis was given independently by Hodgkin & 

 Rushton (66) and by Davis and Lorente de No (cf 88). 



Since individual cardiac cells are only about 100 

 M long and 1 5 /li in diameter, the existence of injury 



currents in cardiac tissue (cf. 25, 26, 69, 105) is pre- 

 sumptive evidence of low resistance electrical con- 

 nections between cells and of intercellular elec- 

 trotonic properties. However, the matter was settled 

 definitely in the affirmative in 1952 by Weidmann 

 (126), who analyzed current spread in Purkinje 

 fibers by means of the cable equation. This analysis 

 yielded values of specific membrane capacitance and 

 resistance, and specific resistivity of myoplasm. The 

 membrane capacitance was 12 /jF cm-, the membrane 

 resistance was 2000 t2-cm-, and the specific resistivity 

 of the myoplasm 105 O-cm, nearly twice that of 

 Tyrode's solution. This resistivity is typical for all 

 plasm and shows that there are no high resistance 

 barriers to current flow in the myoplasm. The current 

 must flow between cells since the space constant was 

 2.0 mm, many times the length of any cell. Therefore, 

 it seems probable that intercellular transmission in 

 cardiac tissue is by local circuit flow. However, the 

 argument for local spread would be much stronger 

 if the means by which current flows from cell to cell 

 without appreciable loss could be given in detail. 

 Aside from the fundamental importance of the prob- 

 lem, a discussion of it is of some interest because 

 Sperelakis, Hoshiko, and their colleagues (109) have 

 contended that the heart is not a functional syncyt- 

 ium, intercellular conduction occurring by means of a 

 two-way synaptic transmitter process. 



Electrotonic current spread in cardiac muscle is 

 inore difficult to measure experimentally and to 

 interpret theoretically than similar events in nerve 

 or skeletal muscle fibers, because current spreads in 

 two or three dimensions in the heart but in only one 

 dimension in nerve and skeletal muscle. Crill and 

 Woodbury (unpublished experiments, 41) have 

 recently measured and analyzed the spread in two 

 dimensions of a current applied to rat atrial cell. 

 Their main experimental findings, which confirm 

 and extend those of Weidmann, are as follows: a) 

 An intracellularly applied current produces appre- 

 ciable transmembrane potential changes in what 

 must be diff"erent cells, b) Current spreads about 

 twice as far in the fiber direction as it does at right 

 angles to fiber direction —i.e., isopotential contours 

 are roughly elliptical with the long axis in the fiber 

 direction (fig. 29). c) The decline of the steady-state 

 potential with radial distance from the current apply- 

 ing electrode is steeper than exponential, as would 

 be expected for a point current source spreading out 

 in two dimensions (fig. 30). 



If impulses spread by local current flow, then the 

 conduction velocitv should be about twice as fast in 



