278 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION I 



FIG. 28. Effects of sympathetic nerve stimulation on the 

 transmembrane potential of a frog sinus venosus cell. Bath 

 contained atropine sulphate do"') to block cholinergic ac- 

 tivity. Stimulation of vagosympathetic trunk at ao/sec during 

 period of interruption of the lower viihite line. Ordinate: 

 transmembrane potential in millivolts; abscissa; time in 

 seconds. (From Hutter & Trautwein (76).] 



The effects of epinephrine on various parts of the 

 heart have also been studied (36, 48, 99, 134). The 

 effects of sympathetic stimulation and epinephrine 

 can be explained by assuming that the transmitter 

 facilitates the Na+-carrying system so that gN.i is 

 always above normal. The possibility that the sympa- 

 thetic transmitter decreases gK is probably eliminated 

 by Harrisand Hutter's (cf. 72) finding that K*- efflu.xes 

 are not affected. However, in dog atrium, application 

 of epinephrine consistently increases the membrane 

 potential (36). Although the mechanism is not known, 

 sympathetic stimulation increases the heart rate. 



Excitation-Contract 10)1 Coupling 



Roughly speaking, depolarization turns on the 

 contractile process and repolarization turns it off. 

 The time from the moment of stimulation to the 

 peak of the contractile tension is proportional to the 

 duration of the action potential. The term "excita- 

 tion-contraction (E-C) coupling" refers to the events 

 which form the link between depolarization and 

 contraction. When Iap is altered by changing ts, 

 contraction time (tc) is about equal to Iap in frog 

 ventricle (Brady, unpublished records); in cat papil- 

 lary muscle tc is about 0.5 of t^p [(117); see also 

 (102)]. Further, the Qm of Iap and tc are equal in 

 frog ventricle [see also Kaveler (82)]. 



The steps intervening between depolarization and 

 contraction are not known, although a number of 

 recent observations give some indication of the nature 

 of the process. Huxley & Taylor (79) found that 

 local depolarization of a frog skeletal muscle fiber 

 membrane in the region of a Z band causes a con- 

 traction of the two half I bands on either side of the 

 Z line — i.e., the A bands mo\e toward the Z band 

 and the I Ijands are obliterated. Equal depolariza- 



tion at other regions has no effect on the contractile 

 material. Although later evidence (78) shows that 

 the Z band is not the main intracellular structure 

 involved in E-C coupling in all skeletal muscle, these 

 findings indicate that specialized structures, perhaps 

 the endoplasmic reticulum, connect the membrane 

 and the contractile material. 



Ltittgau & Niedergerke (89) have examined in 

 detail the well-known antagonism between Ca+"'' 

 and Na+ as they affect the contractile strength of 

 frog ventricular strips. It has been long known that 

 removal of Ca++ from the bathing medium abolishes 

 contraction without appreciably affecting the action 

 potential (cf. 13). Liittgauand Niedergerke found that 

 the peak tension developed during a normal contrac- 

 tion and during KCl-induced contractures is deter- 

 mined almost wholly by [Ca++]o [Na+Jo". Also the 

 amount of depolarization needed to produce a given 

 tension is reduced by a decrease in [Na+]o or an 

 increase in [Ca++]o. Ltittgau and Niedergerke in- 

 terpret their findings as evidence that the contractile 

 tension is determined by the concentration of a Ca++ 

 complex (CaR) in or near the membrane and that 2 

 Na+ ions can also combine with R to form an inactive 

 complex. The effects of ions on the amount of de- 

 polarization required to produce a given tension are 

 explained bv assuming that R has a large anionic 

 charge and that depolarization allows more negatively 

 charged CaR complex molecules to move to the 

 inner side of the cell membrane, where they are 

 effective in initiating contraction. Increasing [Ca++]o 

 and decreasing [Na+]o would increase the concentra- 

 tions of the CaR complex outside and inside the mem- 

 brane so that a lesser depolarization could initiate 

 contraction despite the adverse membrane potential 

 gradient. Thus it appears that one step between 

 depolarization and contraction is the movement of a 

 Ca++ complex to a region, presumably inside the 

 membrane (including the endoplasmic reticulum?), 

 where it initiates contraction; the greater the con- 

 centration of CaR in this region, the greater the 

 tension developed, other things being equal. Further 

 evidence for the penetration of the CaR complex 

 during contraction is pro\ided by the findings that 

 the uptake of Ca++ in muscle is an inverse function 

 of [Na+]o and is a direct function of [K+]o during 

 contracture (96, 97, 116). Also Weidmann (132) 

 has found that an increase in [Ca++]o during the 

 action potential increases the strength of contraction. 

 Considerable progress in this field can be expected 

 in the next few years. 



