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would be caused to flow by alterations in the ionic permeability that are 

 produced in the specific inhibitory patches under the influence of the in- 

 hibitory transmitter substance. With central synapses the nature of these 

 permeability changes has been investigated by changing the ionic composition 

 of the postsynaptic cell. Thus, electrophoretic injection of chloride ions into 

 motoneurons (Coombs et al.. 1955b) or into the cells of Clarke's column 

 (Curtis et al.. 1958) causes the i.p.s.p. to change to a depolarizing response 

 (Fig. 7a to 7b). This inversion of the i.p.s.p. would be expected if the inhibitory 

 transmitter acted by making the inhibitory patches highly penneable to 

 chloride ions, which, under such changed conditions, would exhibit a net 

 flow outward down their electrochemical gradient, so depolarizing the mem- 

 brane. For example, if the normal flux of chloride ions across activated 

 inhibitory patches could be represented as in Fig. 7g, an increased internal 

 concentration of chloride would cause reversal of the net flux, as in Fig. 7h, 

 hyperpolarization giving place to depolarization. 



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Fig. 7. a and b are i.p.s.p.'s, c and d are e.p.s.p.'s generated in a biceps-semi- 

 tendinosus motoneuron by afferent volleys as in Fig. 1 . a and c were first recorded, 

 then a hyperpolarizing current of 2 , 10 >* A was passed for 60 sec through the 

 microelectrode, which had been filled with 3 m KCl. Note that following this 

 injection of chloride ions the i.p.s.p. was converted from a hyperpolarizing (a) 

 to a depolarizing response (b), while the e.p.s.p. was not appreciably changed 

 (c and d). Passing a much stronger hyperpolarizing current (4 ; 10"** A for 

 90 sec) through a microelectrode filled with 0-6 m K2SO4 caused no significant 

 change (e-f) in either the i.p.s.p. or the later e.p.s.p. g and h represent the 

 assumed fluxes of chloride ions across the membrane before (g) and after (h) 

 the injection of chloride ions, which is shown greatly increasing the efflux of 



chloride. 



In the original investigation (Coombs et al., 1955b) it was also found that 

 electrophoretic injection of several other anions (bromide, nitrate and thio- 

 cyanate) changed the i.p.s.p. to a depolarizing response as in Fig. 7b, while 

 such anions as sulphate (cf. Fig. 7e, f), phosphate, acetate and bicarbonate 

 had no such effect. These observations have now been confirmed and extended 

 to many other anions (Araki et al., 1961). The activated inhibitory patches 

 exhibited about the same degree of permeability to eleven species of anion 



