90 PAUL FATT 



hyperpolarization begins to rise on a time course determined by the charging 

 of the membrane capacity, but after reaching a maximum dechnes to a lower 

 level in about 50 msec at which it is then maintained (Fatt and Ginsborg, 

 1958). The delayed increase in membrane conductance on hyperpolarization 

 which tliis reveals is influenced by procedures which change the internal 

 Ch concentration of the fibre. Although the immediate effect of removing 

 CI from the bathing solution is slight, there being usually a decrease in 

 the conductance increase produced for small hyperpolarizations but not for 

 large ones, after soaking the muscle for 1 hr in a Ch-free solution the increase 

 in conductance on hyperpolarization is nearly abolished. In another experi- 

 ment the muscle is soaked in a solution of high K+ concentration for about 

 30 min, it is then returned to the normal low K+ solution, and after the 

 resting potential has recovered the increase in conductance on hyper- 

 polarization is found to be increased greatly. In this experiment an increase 

 in the internal CI" concentration would have been produced by keeping the 

 muscle in the high K ' solution. The conclusion is drawn that the conductance 

 increase on hyperpolarization results from an increase in membrane per- 

 meability toward CI" ions, with the internal CI" concentration having the 

 major influence because of the fact that on hyperpolarization the net move- 

 ment of a negative ion would be outward. (The difference in the effect of 

 internal and external CI" would be accentuated by a movement through 

 long pores whereby all the ions contained in a given pore would have to 

 move simultaneously in the same direction.) 



This conductance change has no apparent role in the function of the 

 muscle fibre, and is thought of as an accidental property of the membrane. 

 A conductance increase on hyperpolarization has been observed in other 

 types of cells, and has sometimes been described as a breakdown of the 

 membrane brought on by the excessive potential difference across it. For a 

 membrane potential of 100 mV across a membrane thickness of 100 A 

 (indicated by examination with the electron microscope) the average field 

 strength within the membrane is calculated to be 10'^ V/cm. Dielectric break- 

 down occurs in most materials at about this field strength, but this cannot 

 be evoked here since it entails the freeing of electrons to conduct the current 

 and this will only occur if there is a total potential difference of at least a 

 few volts available. One therefore has to consider a less elementary process, 

 in which the field causes a charged molecular component of the membrane 

 to be moved, the electrical energy being used to break chemical bonds by 

 which this component is held in its normal position. The structure in question 

 is pictured as acting as a plug, which on being moved from its normal position 

 leaves holes through which ions in the solutions bordering the membrane 

 are able to diffuse. Finally, it is suggested that the inhibitory transmitter 

 operates by breaking the same bonds through a chemical reaction — the 

 reaction involving the receptor body situated on the outer surface of the 



