ur Jaqlou? lsure8B alsJado 01 JIASIT uoxE eql olq apoJpala aus B aJnpoJlur o] uoltprBdaJd stql qlr^\ elqrssod aq lqSru u leqt (aror ) a1o3 'S ypuesurnJ'f .Hols?11a,lrsz (oaer).{a1xng 'g 'y puz (salqg u113pog ot parrncro ll alerqalre^ Jo esoqt ueqt ra8.re1 saru1l d*$ a.re suo,tcas-ssorc iioq,n tpodoieqdac iql 3'o sarqg-a,,r.reu luer8 eql o] uopuaue ur,tu.rp Suraeq EunoS .7 .f 'la sJl ,tuaurSas plnorrr eTds eqt os puu txeu aql ur aslndurr qsa.r3 e ;o uorle.raua5 aql roy parrnbar tuatx? ue 01 palrcxa aqt "aJE Jo p?aqe auerquau aqt sazrrelodap dypnpe aspdu.rr alJau oqtr .eqnduu t?ql pa^roqs urlSpog u?lv 196l u1 ue 3o a5zssud aql uo a^Jsu 5rl1 JO Uorpas-ssoJc eql ]3 apoJpala puocas B o1 a r]ElaJ uorxagap a,rrle3au e poJalsr8al aprslno aql uo apoJtoala ue asnecaq uoBarl"^ a,rr1zSau aql lua^a srqt palp, pzq ,aslndurr alJau aql Jo alnl?u l?orJlcala aqtr Jo leJa^ocsrp .prrout,(ag 'o.raz -slog nO saqceoldde tuautorrr u .ro.; 1zr1ua1od auurq eql -ruaru luql os (acuepnpuoc Jo as"arcur uu) flqrqearu.rad .;o es"-aJrur alqrsJa^al uappns a sr luaJlnc pcrJpela Suzr.rrlodap e- gas ,{q dn aslnduu .ro 1zr1ua1od uorlcu aq1 leql pafelnlsoa Arorql .,{ayxn11,urr13po11 s.uarsruag ( p.re.rag'8uag,sau.(ay ) sluaurat?ts asaql qsrlqBtsa ol papaau uaaq sEq ^\aJ l?ql 1"roar luluaurlredxe Jo lunoue .(.rzurp.roe.r1xa aql ,rlar^al ol aJaq .+ualuoc alqrssodurr s.r lI runrsselod s1r f,q paurut.ralap dgarqc plnom uoxe aql ]Q Jo aplslno pu? (a,rrle8au) aprsut aqt ueal$.laq ('A[I of-) IEuua]od Surtsar er[J 'uox" aql ur runrsszlod.prng JEJnllacBJlxJ aql ur uort?riuecuoc q8rq ur luasa.rd sr unrpos 'aptrolqc pue urnrpos o1 .,(lrpqeau.rad,ro1 .(.ra^ s?q lnq urnrsselod ol alq?eurad sr auzrquau a^lau arll .(zoot) uolrerrcxa go ,{roaql s.ualsu.rag }uauotu z ro3 1pcj.r o1 .{rzssacau'.uou sr l; uoqcy srldBuds uo uor?BrrrJoJul .eprsul 9 ralduqC 116 CHARLES sCoTT SHERRINGToN the extracellular fluid (or a corresponding artificial solution) and so procure direct evidence as to what actually happens across the nerve membrane during impulse initiation. They were rewarded by the unexpected discovery that the nerve-action potential exceeded the resting potential. On Bemstein's theory the action potential across the membrane ought to have gone, maximally, to zero corresponding to some 7o mV. Actually it swung 30 mV. beyond it to the positive side. Years of exacting work finally led Hodgkin and Huxley to a quantitative theory of the ionic events during the nerve impulse, which is now well supported experimentally. The essential components of the ionic theory are that the sudden increase of conductance elicited by the depolarizing current is a diphasic event, beginning with a transient sodium permeability and changing to a potassium permeability in the falling phase of the spike (or action potential). During the first phase, positive sodium ions from the outside flow into the axon and this process is recorded as the rising spike. In the second phase, the transient sodium conductance is replaced by the potassium conductance during which potassium ions move outward down their concen- tration gradient. The mechanisms responsible for producing and timing the exchange of the two ionic events are unknown, but the sodium conductance increases explosively when the mem- brane has been depolarized to a certain threshold value. Evidence has been presented to the effect that, when an impulse is generated in motoneurones or at the motor end-plate, this process is actually preceded by a slow depolarization. As to sense organs, the author long ago postulated that'generator potentials' would arise in t}tem as a sequence to an initial process possessing specific sensitivity to the adequate stimulus (for instance, a photochemical reaction in the retina). Such generator potentials have since been recorded in several sensory end- organs, but it would carry us far beyond Sherrington's influence on nerve physiology to review this work. Our present concem is with the intracellular recording from motoneurones. In the hands of Sir John Eccles and his colleagues, especially J. S. Coombs, D. R. Curtis, and P. Fatt, this has proved very rewarding and has clarified many of the problems raised in the previous chapters. This method was an offshoot of the 'inside' approach initiated by Hodgkin and Huxley. 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JuBJqurau qtoq urplal or punoJ aft sllal ,suorl?rleuad .salnuru lca.yad qlrd\ ro spuoJss ,{reJ uuqt aJou .roJ slurtualod^ll"cruqca-l eupJquaur " laql Sururelureur .yo alqzdecur eq plno.tr Aeql asuc rallel a-ql u1_.papuno,lr .,(lpur8.rzru .ro passzd_,(q aq .proc 11tu ruaqt 3o_.{tr.ro[ru a3.re1 eq] aql m u.r\op <ieep are iaqr acurs adocsorcrur p ';nq rapun pa.,',tarl aq p1no, sllac aql Jr re8.rer pooi E aprlord plno,^,l slqJ.r/ Og spaacxa.{1a.m.r sqac u.roq I"Iuer{ aqt Jo J3}auplp a5eraae aql .sra{ro^!-oJ slq puE salrf,g .ipo .r:ayad .(q .,(1a,rrsn1cxa pasn aql uy Irn* ,oiirrrar.rd n,ir .Je^rJp-orcrur "q Jo uoB.€xrl Jo pur{ euos .,{q pto.r luurds pasodxa aqr q8no.rqr pacue^p? dlsnorlnzc ,q i.n- drelJduc-o.rcru, arlJ 'sauolnauolou rxo+ spJocal aprsu ur?tqo ol sldura*u ;aluaurrredxa aq] qcrq,rl ur uorJenJrs aql ,rlou JaprsuoJ uo.lr?-elcsnul aq1 surp.rocar,r, oro""'$fiJ"';il'11;:i6X1J soruorpale aql pa,ro.rdur :aprsr, Jo (oeot ) url5pog prr, 1n1sr51 eql ulo{ ppualod Surlsar eql proJar o} snql pu? sarqu aTosnur Jo aueJqueu aqt alerlauad ol pasn aq plno) r/ 9.o atoleq sdrl ql1aa. sa1;e11dec-oJcru l?qt punoJ ppq.(aqa .alqrsuodsa.r ara,n (o*ot) p.re.rag pur 3ur1 pue (s+or) prrrrg pu, *rqrrg qcrqrr JoJ anDruqral epoJtcalaoJctru aql;o luaura,rordurr aql pasoddns III NOTJsV srIdvNrs No NorrvfiuoJNr .gqtsNr, I I8 CHARLES sCoTT SHERRINGToN of the order of a few millivolts, that had been recorded just outside the cell becomcs enormous by comparison and positive, because from the new base line of, say, 70 mV. it goes to zero by producing +7o mV. and adds a- positive 'overshoot' of some 20 to 3o mV., as explained above for the axon of the squid. These events are illustrated in Plate t l. Each antidromic spike is accompanied by a sharp report from the loudspeaker adding a dramatic touch to the proceedings. With many a successful pcnetration the size of the spike improves for a while and the membrane potential gradually increases, apparently due to sealing up of initial leaks arorurd the penetrating tip. The figure shows that the action potential rises in two steps, an initial slor,ver phase which has been found to be due to the antidromic impulse depolarizing the axon hillock. This suflces to generate a spike there whicir in tum depolarizes the rest of the cell, its soma and part of the dendrites, so that this portion also generates a spike, which is the one illustrated. Thus the tip of the microelectrode inside the soma can only 'see' the spike in the soma itself; the invasion of the axon hillock it records as an initial depolarization because the spike itself is too far away. Thus the motoneurone, in generating an impulse, behaves in principle like the membrane of the giant axon of the squid Loligo, which was used by Hodghin and Huxley in the experi- ments tllat led to the formulation of the ionic theory of excita- tion.