JEAN BOTTS 9 I 



longed (31). Other substances may enhance contraction, and this may occur 

 with or without a marked alteration in the action potential. For example, 

 another quarternary ammonium ion has given interesting results when applied 

 to frog sartorius muscle. It is found that when sodium ions are partially replaced 

 by tetraethylammonium ions in the external medium, the height of the action 

 potential is reduced (though not to the extent predicted solely by sodium 

 dilution), the declining phase of the action potential is prolonged, and the iso- 

 metric twitch tension is enhanced — both in magnitude and duration (39). The 

 membrane conductance during the declining phase of the action potential is 

 somewhat smaller than normal. These results suggest that one of the main 

 effects of this substituted cation is a reduction of the increase in the active 

 membrane permeability to potassium (39). 



However, a similar enhancement of twitch tension can be achieved with little 

 or no alteration in the action potential. Extensive work has been done on sub- 

 stances which bring about these tension changes since such investigations offer 

 promise of elucidating connecting links between excitation and contraction. Of 

 special interest are the studies of Kahn and Sandow (56, 57) and of Hill and 

 JMacPherson (45) on anions. When bromide, nitrate, or iodide are substituted 

 for chloride in Ringer's solution, again a considerable enhancement and pro- 

 longation of the twitch tension in frog sartorius muscle are observed. The 

 tetanus tension in these preparations is unchanged, and until lately no change 

 had been observed in the action potential (56, 57). Recently, however, Etzen- 

 sperger (29), applying an internal microelectrode to frog sartorius muscle, has 

 reported that although the resting potential and spike potential are unchanged 

 by these abnormal anions, there is a detectable prolongation of the negative 

 after-potential. 



The anion effect on tension increases in the order CI < Br < NO3 < I. Cal- 

 culations of diffusion times of ions into the inter- and intra-fiber spaces indicate 

 that tension augmentation is essentially complete before the anions have had a 

 chance to penetrate the fibers extensively (45). Also, after long equilibration of a 

 muscle in one of the substituted-anion Ringer solutions, a return to the normal 

 chloride medium causes a rapid loss of the augmented response (correlated with 

 the anion exchange in the extracellular fluid), even though the abnormal anion 

 concentration within the fiber has not yet decreased appreciably (45). It is 

 therefore presumed that the anion effect on contraction is mediated at or near 

 the fiber membrane and is not a direct effect on the contractile mechanism itself. 

 Hill and MacPherson (45) have found that the amount of heat production 

 associated with a twitch in the abnormal anion medium is roughly proportional 

 to the magnitude of the contraction. Fibers contracting repetitively in NO3- 

 Ringer fatigue more readily than fibers similarly stimulated in Cl-Ringer 

 solution. However, if a fiber in Cl-Ringer is stimulated in such a way (two 

 closely spaced stimuli, delivered repetitively) as to induce a mechanical response 



