CELLULAR ELECTROPHYSIOLOGY OF THE HEART 



239 



Cranefield (27, 68). Shanes (106) has exhaustively 

 reviewed the electrophysiological literature from a 

 viewpoint provided by the ionic theory and some 

 of his own interesting ideas. 



THE RESTING CELL MEMBR.^NE 



The heart, like any other tissue, is composed of 

 more or less homogeneous cell groups and the inter- 

 stitial fluid bathing them. Cell plasm is separated 

 from the interstitial fluid by a thin electrically 

 insulating membrane. This membrane separates 

 aqueous solutions having the same total osmotic 

 pressure but radically different compositions. The 

 extracellular fluid has high concentrations of Na"*" 

 and Cl~ and a low concentration of K+. The situation 

 is reversed in intracellular fluid, and the anion 

 component consists largely of organic acid radical and 

 phosphate ions. Of course, many other substances are 

 also dissolved in the aqueous phases, but attention 

 here will be focused principally on Xa"*", K+, and Cl~, 

 since these are the only ions carrying appreciable cur- 

 rents through the membrane. In addition, there is a 

 potential difference of about 80 mv (inside negative) 

 across the membrane. Since the membrane is exceed- 

 ingly thin, it is apparent that large concentration and 

 potential gradients exist across it. Two properties of 

 the membrane lead to the development and mainte- 

 nance of the transmembrane ion and potential gradi- 

 ents, a) The membrane's structure permits ions to 

 diffuse through it at only a minute fraction of the rate 

 at which they diffuse through water. In most cell 

 membranes at rest, Na"*" diffuses through the mem- 

 brane much more slowly than K+ and Cl~ do. b) 

 Energy derived from metabolism is used by the cell to 

 transport Na"*" out of it and K+ into it. By balancing 

 the inward diffusion of Na+ and the outward diffusion 

 of K+, this active transport maintains the low Na+ 

 and high K+ concentrations inside the cell and the 

 transmembrane potential. 



Since the transmembrane potential is generated by 

 the separation of charges resulting from differential 

 ion movements through the membrane, this discussion 

 deals mainly with the factors governing the move- 

 ments of ions. The three prime factors are /) the 

 permeability of the cell membrane to ions, 3) the ion 

 and potential gradients across the membrane, and j) 

 the active transport of ions. 



Passive Ion Movements 



MEMBRANE STRUCTURE (39, 103). The Cell clcctrical 

 membrane probably consists of alternating layers of 

 lipids and proteins. In the lipid layer, the long thin 

 molecules are closely packed with their long axes 

 parallel and oriented perpendicular to the membrane 

 surface. Each lipid layer is two molecules thick, the 

 nonpolar ends of a pair of molecules being opposed 

 and their polar ends being bound to the protein 

 layers. The unit of membrane structure is probably a 

 bimolecular lipid layer between two monomolecular 

 protein films, 8.5 nin thick (39). Electrical and elec- 

 tron micrographic measurements indicate that the 

 membrane is only about 10 nm thick; hence this 

 structure is composed of one or at most two structural 

 units. 



Since lipids are hydrophobic, water and water- 

 soluble compounds probably cannot penetrate a well- 

 organized region of the membrane. It is more reason- 

 able to assume that the lipid phase is interrupted by 

 water-filled pores of small diameter which perforate 

 the membrane; ions could readily diffuse through 

 such pores. The low permeability of the membrane 

 to ions could indicate a paucity of pores and its lower 

 permeability to Na+ than to K+, and Cl~ could indi- 

 cate an average pore size slightly larger than the 

 latter two ions and slightly smaller than Na"*" [see 

 Solomon in (100)]. Even so, all phenomena of ion 

 transport cannot be explained on the basis of mem- 

 brane porosity and it is also necessary to postulate 

 ''carriers" within the membrane. Regardless of the 

 exact mechanism by which ions pass through the 

 membrane, the rate of their passive penetration de- 

 pends directly on the gradients of both concentration 

 and potential. The specialized properties of the inter- 

 calated disc membrane will be considered in the sec- 

 tion on intercellular transmission. For the discussion 

 of intracellular events, the cardiac cell membrane 

 may be regarded as a homogeneous structure. 



MEMBRANE CAPACITANCE AND RESISTANCE (66, 88, I 1 3, 



126). A capacitor consists of two conductors separated 

 by an insulator. A cell is a capacitor: the interstitial 

 fluid and cell plasm are conductors, and the mem- 

 brane is an insulator. The capacity of a capacitor is 

 defined as the ratio of the charge (q) on either con- 

 ductor to the potential difference (S) between the 

 conductors, C = q/S. By definition, the electric 

 potential difference between two points is the amount 

 of work done against electrical forces to carry a unit 

 positive charge between the points. The electrical 



