306 PHYSIOLOGY OF INDUCED HYPOTHERMIA 



tional to the log of the extracelkilar K concentration-'' hut is not appreciahly influ- 

 enced hy even a complete ahsence of extracellular Na/" 



The menihrane potential changes associated with activity are somewhat more 

 complex in nature. It has been demonstrated that, in the squid giant axon, the 

 upstroke of the action potential results from a specific change in the Na permeabil- 

 ity of the membrane and a resulting inward (positive) current carried by this ion/^ 

 Repolarization, in turn, results from a sul)sequent decrease in Na permeability and 

 rise in K permeability;" the resulting net outflow of positive charge carried by K 

 ions restores the resting transmembrane potential to normal values. 



In cardiac muscle, although evidence for changes in ionic permeability and ionic 

 fluxes during activity is less direct, it is probable that the upstroke of the action 

 potential similarly results from a change in membrane permeability and inward 

 sodium current.^-'- ■^° It has been demonstrated that, during the upstroke of the 

 action potential, the membrane resistance of Purkinje fibers is decreased to approxi- 

 mately 1/100 the resting value.-* Furthermore, a decrease in the concentration of 

 extracellular Na results in a marked drop in the rising velocity and magnitude of 

 the action potential but fails to influence the resting potential.^"' ^^ Also in agree- 

 ment with this mechanism is the similarity between the magnitude of the reversed 

 membrane potential at the peak of the action potential (inside positive with respect 

 to outside) and the potential difference which might be expected from a Na activity 

 ratio of 1 : 10 across a membrane exclusively permeable to this ion. 



The mechanism responsible for repolarization of the cardiac fiber membrane is 

 poorly understood. Recent evidence suggests that the descending limb of the initial 

 spiked reversal is a result of a decrease in Na permeability.^- However, although it 

 has been demonstrated that activity in cardiac muscle is associated with an increased 

 net loss of K and that most of this loss occurs during or shortly after the action 

 potentiaP' there is no direct evidence for an increase in K permeability during re- 

 polarization. Measurements of membrane resistance suggest that ionic conductance 

 is decreased below normal values all during the plateau and that there is no appre- 

 ciable increase in conductance during the repolarization limb of the action po- 

 tential.^^- ^^ Also difficult to evaluate are the results of recent experiments which 

 show that a sudden increase in the concentration of K outside the fiber results in a 

 shortening of the plateau and accelerated repolarization. ^^^ 



In summary, the following hypothesis might be proposed to explain the potential 

 differences recorded across the membrane of cardiac muscle fibers. The resting po- 

 tential depends most directly on the potassium concentration gradient and appears to 

 result from the greater tendency of this ion to diffuse outward across the mem- 

 brane. The contribution of sodium to this potential is small because of the relative 

 impermeability of the resting membrane to Na. With depolarization there is a large 

 and specific increase in permeability to Na and the resulting inward sodium current, 

 driven by both a concentration and potential gradient, is responsible tor the rapid 

 upstroke of the action potential and the reversal of polarity or overshoot. The 

 descending limb of the reversal results from a decrease in Na permeability to rest- 

 ing values. During the plateau the membrane is only sparingly permeable and no 

 large change in potential is recorded. Repolarization may be the result of an outward 

 K current but additional evidence in support of this process is needed. 



