CELLULAR ELECTROPHVSIOLOGV OF THE HEART 



247 



axons, recovery is hastened by a delayed, depolariza- 

 tion-induced increase in Pk- At about the time Pn„ 

 begins to fall, Pk starts to increase at an appreciable 

 rate, so that repolarization is speeded. The increased 

 Pk persists for some time after S has reached the 

 neighborhood of S,. Since Sk is considerably more 

 negative than Sr, S goes almost to 6k and then slowly 

 falls back to Sr. 



The action potential is generated by the move- 

 ments of Na+ and K+ ions through the membrane 

 successively and respectively discharging and re- 

 charging the membrane. Hence, Auns and Amk are 

 the immediate sources of energy for the generation of 

 the action potential. The ionic interchanges during 

 an action potential slightly increase [Na+J, and 

 decrease [K+]i. The increased [Na+]i stimulates the 

 Na'*'-K+ pump, and the excess Na"*" ions are extruded 

 over a long period of time. It should be emphasized 

 that Na"*" pumping is not the cause of the repolariza- 

 tion phase of the action potential. Aside from the fact 

 that Na^-K"*" pumping is neutral, the process is much 

 too slow. For example, the active efflux of Na+ from a 

 quiescent skeletal muscle cell in i sec is of the order 

 of the influx of Na"*" during one impulse lasting about 

 I msec. 



An impulse is propagated by means of local current 

 flow between active and inactive regions (see 112). 

 Current flows in closed loops: out of the membrane 

 at an inactive, polarized region, through the inter- 

 stitial space to an adjoining active region, into the 



membrane and back through the intracellular fluid. 

 Outward flow of current depolarizes the inactive 

 membrane. If strong enough, the current eventually 

 brings the membrane to threshold and this region also 

 becomes active. This process is repeated at successive 

 regions of the fiber so that the sequence of excitation 

 and recovery moves along it continuously at a con- 

 stant speed. 



Membrane Current 



The propagation of an impulse is accomplished by 

 a depolarizing current supplied by an adjacent active 

 region. With respect to a particular small patch of 

 membrane, this depolarizing current comes from an 

 external source and is indistinguishable from current 

 supplied by a stimulating electrode. Any external 

 current (I,„) flows through the membrane via two 

 pathways (fig. 3^4) : the capacitor — the current (Ic) 

 going to change the charge on the membrane — and 

 the resistor — the current (li) being carried through 

 the membrane bv ions. Thus 



In, 



Ic -I- I, 



(7a) 



During propagation of an impulse Im and Ic result 

 from changes in li induced by voltage and time-de- 

 pendent changes in membrane ionic permeabilities. 

 Thus the study of membrane excitable properties 

 reduces to a study of the determinants of permeability. 

 In turn, permeabilities are estimated from measure- 



FiG. 3. Two approximate equivalent circuits for i cm- of cell membrane showing the division of 

 an applied current between the various components. A: the e.Kternal current (Im) divides between 

 the membrane capacitance (Cm) and resistance (Rm). Current flowing through the capacitor (Ic) 

 charges the membrane; current through the resistance indicates the flow of ions (li) through the 

 membrane. Therefore, !„ = Ic -f- Ii = Cmde/dt -f- (S — £r)/Rm. B: ionic current is divided into 

 its three major components, iNa -|- Ik -|- loi = Ii. Rk, Rci, and Rns are the resistances to K, CI, 

 and Na ions, respectively; 6k, Eci, and Sms are the equilibrium potentials of these ions. Rnb and Rk 

 change with voltage and time, as indicated by the arrows through their symbols. [After Hodgkin 

 & Huxley (60).] 



