CELLULAR ELECTROPHVSIOLOGV OF THE HEART 



243 



TABLE I . Approximate Steady State .Vfl+, A'+, and Cl~ 

 Concentrations and Potentials in Frog 

 Ventricular Muscle* 



* Values for Na"*" from Hajdu (51 ) and Johnson (81 ) ; 

 those for K^ from Hajdu, and those for CI- and potentials 

 from Brady & Woodbury (4). 



t Calculated for an action potential duration of i sec 

 and an interval between beats of 3 sec. 



X Calculated from [Cl-]„ and Gci, assuming that Eci =£. 



§ Calculated from IQ-^ ■''*, the equilibrium ratio for a 

 univalent cation. 



mechanical properties of the heart accompanying the 

 transition from rest to activity may result from net 

 CI- movements. 



Sk is 10 mv more negative than the diastolic mem- 

 brane potential and 40 mv more negative than the 

 average potential, indicating that [K+Ji is higher 

 than would be expected from the Nernst equation. 

 The diflference between Sk and Sr is of doubtful signifi- 

 cance considering the uncertainties in the values of 

 both. However, the proper comparison is between 

 Sk and S, and this difference is highly significant. 8k 

 is significantly greater than Sr in a number of tissues 

 including nerve (64), skeletal muscle (i), and moto- 

 neuron (38). The finding that [K+], is higher than the 

 equilibrium value means that there is an influx of K+ 

 against the electrochemical gradient, i.e., from a lower 

 to a higher potential energy. This influx must occur; 

 otherwise, [K"*"]! would not remain constant in the 

 face of the relatively high permeability of the mem- 

 brane to K+ and the consequent net outward diffu- 

 sional flux of K"*". This passive efflux must be equalled 

 by an equal influx of K+ driven by other than diffu- 

 sional and electrical forces. This excess influx is 

 called active K"*" transport. 



The distribution of Na+ is far from electrochemical 

 equilibrium. Both the concentration and potential 

 gradients act to drive Na+ into the cell. From table i 

 it can be seen that the cell interior must be made 46 

 mv positive to the outside to establish electrochemical 



equilibrium for Na+. Since Na+ can penetrate the 

 membrane (cf 46, 34, 64, 81), unspecified forces must 

 be driving Na+ out of the cell. This efflux must match 

 the influx due to the concentration and potential 

 gradients. Dean (30) in 1941 clearly delineated the 

 need for this active Na+ transport and considered the 

 implications of a simple model. 



Active Xa'^ — A'+ Transport 



ACTIVE TRANSPORT. From the foregoing, it appears 

 that potential and concentration gradients are not the 

 only factors which determine the net transmembrane 

 flux of an ion. For example, a pressure gradient across 

 a membrane could markedly alter ion distributions 

 because the resulting flow of water would probably 

 drag ions with it. However, bulk flow is probably not 

 significant in nonsecretory cells. Similarly, a large net 

 flux of one solute could drag along another solute, 

 particularly in long narrow membrane pores (65). In 

 addition, Ussing (124) has proposed a mechanism 

 which would increase, equally, the efflux and influx 

 of an ion independently of electrochemical gradient. 

 This mechanism, called exchange diflfusion, requires 

 the existence of a carrier substance in the membrane 

 which combines selectively with an ion species and 

 which can move through the membrane only when 

 associated with an ion. Thus a round trip of the 

 carrier could result in the exchange of an external for 

 an internal ion. Keynes & Swan (85) have substantial 

 evidence from tracer experiments that exchange 

 diffusion accounts for about half of the efflux of Na"*" 

 from frog muscle. If the exchange efflux is subtracted 

 from the total efflu.x, there still remains a considerable 

 efflux which is not attributable to passive forces. This 

 Na+ efflux and a substantial part of the K+ influx are 

 against their respective electrochemical gradients and 

 so these fluxes require the continuous expenditure of 

 energy for their maintenance. Ultimately, this power 

 must come from cellular metabolism. Any flux which 

 is maintained by a direct expenditure of energy may 

 be defined as active transport. However, this con- 

 ceptual definition is not very u.seful. A limited but 

 more useful definition is given by the Ussing flux 

 ratio test (123). If, after any fluxes due to exchange 

 diflfusion are subtracted, an ionic species does not 

 satisfy this equation, it is assumed to be actively 

 transported. The flux ratio equation can be derived 

 from ecjuation 2c. The influx (Mg") and efflux 

 (M's"') are calculated successively by setting [S]i 

 and [S]o equal to zero in equation 2c. Both fluxes 



