124 PHYSIOLOGICAL TRIGGERS 



may therefore be endowed with extraordinarily sensitive, but gradedly re- 

 sponsive membrane transducing electrical fields into permeability changes with 

 considerable amplification. The highest known amplification appears to be in 

 the thermal receptors of snakes (27). 



A general scheme of transducer electrogenic action in sensory receptors is 

 the following: 



Stimulus — ^ Transducer action — >• Electrogenic action 

 Specialized — > Permeability change in specialized -^ Membrane potential change (2) 

 membrane sites 



Electrically Excitable Tissue 



a) Spike Generator. A very different type of response might be expected if 

 the transducer membrane is electrically actuated and operates according to 

 the scheme: 



Stimulus — ^ Transducer action — > Electrogenic response 



Membrane depolarization — > Membrane permeability — > Membrane depolarization 

 > change 



Positive feedback 



(j) 



Once initiated, depolarizing electrogenic activity would tend to cause further 

 change in the membrane permeability and additional membrane electrical 

 change. The process would therefore exhibit regenerative action and an ex- 

 plosive response. An electrical analog of this system is the bistable electronic 

 circuit. A trigger' potential change tends to drive this circuit from one level of 

 output voltage to another with no intermediates. While exhibiting this all-or- 

 none property, the response of axons and of many muscle fibers lasts only a 

 characteristic, brief and remarkably constant time, and then returns to the 

 initial condition. This behavior is analogous to a monostable electronic circuit, 

 in which the bistable condition is suppressed by a capacitative leak circuit. 



Hodgkin and Huxley (no) have postulated in the specific terms of a bio- 

 logical membrane a sequence of analogous events. Initial increase of sodium 

 conductance by a depolarizing stimulus drives Na+ inward, depolarizes the 

 membrane still more and this regenerative process rapidly brings the membrane 

 to the reversed 'sodium potential.' The 'leak' is provided by two additional 

 processes, also potential-determined, but proceeding at slower rate. 'Sodium 

 inactivation' decreases the heightened sodium conductance, while potassium 

 conductance increases to drive this ion outward, dissipate the reversed charge 

 and restore the membrane potential to its resting value. 



Elegant experimental and mathematical tools enabled Hodgkin and Huxley 

 to deduce the time course of the postulated membrane conductance changes 

 during the squid spike. This sequence also explains satisfactorily a number of 



