"Slow" and "Fast" Muscle Fibers

ERNEST GUTMANN Department of Physiology and Pathophysiology of the Neuromuscular System, Institute of Physiology, Czechoslovak Academy of Sciences, Prague

The great variety of structure and depolarization, but the slow fibers function of different muscles reflects of the frog show a sustained con­ apparently the process of adapta­ tracture during the whole period of tion to different functional de­ reduced membrane potential (Kuf­ mands, but it has remained a source fter, 1946; Fleckenstein, 1955). of confusion, especially if an at­ Thus two distinct fiber types, i.e., tempt is made to find a common fast (twitch) and slow (tonic) fi­ principle of order for this variety. bers do exist in frogs and toads and The terms "fast" and "slow" mus­ related differences have been cle fibers in mammals are used in described for the membrane poten­ reference to their faster or slower tials (Kuffier and Vaughan Wil­ contraction times. Both these mus­ liams, 1953; Kiessling, 1960), ar­ cles, e.g., the fast M. Extensor digi­ rangement of muscle fibrils torum (E.D.L.) and the slow M. ( "Fibrillen" or "Felderstruktur"), soleus of the rat are "twitch" mus­ pattern of filaments and structure cles, i.e., they react with propagated of the sarcoplasmatic reticulum action potentials to nerve stimula­ (Kruger, 1952 ; Gray, 1958 ; tion. Contrary to this, the slow­ Peachey, 1965), and type (focal or tonic muscle fibers of the frog re­ multiple) of innervation. spond with local non-propagated Kruger (1952) claimed that some depolarizations, activating contrac­ mammalian muscles consist en­ tures (Tasaki and Mizutani, 1943; tirely of fibers with "Felderstruk­ Kuffier and Gerard, 1947; Kuffier tur" and that the same distinction and Vaughan Williams, 1953). The between muscle fibers with "Fibril­ normal responses of these "tonic" len" and "Felderstruktur" as in fibers in the body are long-lasting frog muscles could also be made in contractures, which they maintain mammalian muscles. Mammalian in a graded fashion to depolarizing muscle fibers with "Felderstruktur" concentrations of acetylcholine showing only non-propagated junc­ (ACh) or potassium. In fact, local­ tional potentials in response to nerve ized responses to ACh in fast­ stimulation have indeed been found twitch muscle fibers and slow long­ in the extraocular muscles of the lasting contractures in slow-tonic guinea-pig (Hess, 1961). However, muscle fibers have already been de­ in other mammalian muscles such scribed by Rieser and Richter (1925) a distinction has not been found. and Sommerkamp ( 1928). Essen­ Moreover, no distinct structural dif­ tial differences in contracture re­ ferences could so far be detected sponses have been described in the between fast and slow mammalian fast (twitch) and slow (tonic) fi­ muscle fibers. bers of the frog, especially in their Therefore, the question whether reactions to KC! solutions which there are two fiber types or a whole initiate contractures by membrane spectrum of many different muscle depolarizations. A phasic contrac­ fibers as regards structure, innerva­ ture is evoked in fast fibers (Hodg­ tion, speed of contraction and type kin and Horowicz, 1960) , i.e., the of electrical response in mammalian fast fibers of the frog will relax rela­ muscles is still unsettled (Huxley, tively rapidly despite membrane 1964) .

78 MCV QUARTERLY 2(2): 78-81, 1966 E. GUTMANN

A study of the contracture re­ posterior (L.D.P.) and the slow in contracture behavior of dener­ sponses in fast and slow mammalian Latissimus dorsi anterior (L.D.A.) vated muscles is observed after ex­ muscle fibers especially during de­ of the chicken (Gutmann, Jir­ posure to caffeine. After denerva­ velopment should be rewarding. manova and Vyklicky, to be pub­ tion the E.D.L. of adult animals Contractures do in fact demonstrate lished) . The L.D.P. does not react reacts to caffeine with contracture; the main features of the mecha­ to ACh even at highest concentra­ it has thus gained properties of the nisms of the process of excitation­ tions, whereas the L.D.A. reacts at slow muscle (Gutmann and contraction coupling, and the basic relatively low concentrations of Sandow, 1965) . The student of dif­ differences in the contracture re­ ACh with a sustained contracture. ferentiation between fast and slow sponses to different agents in the muscle fibers will find many valu­ two types of muscle fibers in the CAFFEINE CONTRACTURES IN able clues from work comparing frog would suggest important mod­ E.D.L. AND SOLEUS MUSCLE striated and smooth muscle, a line ifications of this process (see San­ OF THE RAT developed successfully, e.g., in re­ dow, 1965). Are there any sugges­ spect to birefringence and other tions for such differentiation also In the E.D.L. of animals 22 to characteristics (Fischer, 1944). Slow in mammalian muscle fibers? 30 days old exposed to a 20 mM muscle fibers and muscles during solution of caffeine, potentiation of early stages of development resem- ACh CONTRACTURES IN E.D .L. twitch tension but no contracture is AND SOLEUS MUSCLE observed (Gutmann and Sandow, 9 SOLEUS 1965). However, contracture re­ tet. OF THE RAT sponses to exposure of caffeine :t Figure 1 shows that in both could be observed until the 18th to ~ ~ E.D.L. and soleus muscles of the 22nd day after birth. No contrac­ EXTENSOR rat (three days old), contractures ture was observed in this muscle of to ACh can be produced. In figures animals more than 22 days old. In 1 and 2 the contracture response contrast to the E.D.L., the soleus :t l~ ~ O Om . HC . L70 .. and the tension developed during responds with contracture also in contracture respectively are ex­ animals one month old. Thus the Fig. I-Maximal isometric tetanic pressed in percent of maximal te­ contracture response to caffeine is contraction (first curve) and con­ tanic tension output of the muscle. lost during ontogenesis in the fast tracture response to acetylcholine (sec­ It can be seen that there is a con­ E.D.L., but not in the soleus mus­ ond curve) added to the bathing so­ siderably stronger contracture re­ cle which maintains sensitivity to lution at a concentration of 5.10-• of sponse in the soleus muscle than this contracture-inducing drug. A M. soleus and M. extensor digitorum in the E.D.L. Moreover, contrac­ similar contracture behavior is ob­ longus of three-day-old rats. Tetani ture is observed at a threshold value served in the Latissimus dorsi of were produced by "massive" direct stimulation in vitro by a 300-msec­ of 10-1 in the soleus muscle, but the chicken. The fast L.D.P. of long stimulus, the single stimuli being at 7.10-7 in the E.D.L. adult animals shows no contracture, square shocks 1.0 msec in duration However, the fast E.D.L. loses whereas the slow L.D.A. responds (see Sandow and Brust, 1958). the capacity to react with contrac­ with a contracture to caffeine (Gut­ tures to ACh about 20 to 25 days mann, Jirmanova, and Vyklicky, 150 after birth of the animal, whereas 1966, to be published) . the slow soleus muscle reacts to maxtet ACh, though to high concentrations NERVOUS INFLUENCES only, with contractures at all stages AFFECTING CONTRACTURE of development. It is interesting to BEHAVIOR OF 50 see that there are considerable dif­ MAMMALIAN MUSCLES ferences in threshold and intensity of contracture response during the It is well known that during de­ 3 6 12 DAYS earliest stages of development that nervation the whole muscle fiber I have studied (Gutmann and becomes sensitive to ACh (Ginet­ Fig. 2-Changes of contracture re­ Hanzlikova, in press). Very marked zinsky and Shamarina, 1942; Axels­ sponse of M. soleus (full line) and M. extensor digitorum longus (inter­ differences in contracture responses son and Thesleff, 1958; Miledi, rupted line) of rats 3, 6, and 12 days to ACh are, of course, known to 1960; and others). Thus the de­ after birth. The contracture response exi~t between fast (twitch) and slow nervated muscle shows the contrac­ is expressed in percent of the maxi­ (tonic) muscle fibers of the frog. ture behavior of muscle at early mum isometric tetanus tension Similar qualitative differences exist stages of development (Diamond (= 100% ), obtained by electrical between the fast Latissimus dorsi and Miledi, 1962). A similar change stimulation in vitro.

79 "SLOW" AND "FAST" MUSCLE FIBERS ble in their reactions the smooth Our first consideration will, of tive amino acids into the proteins muscle. The comparative approach course, be centered on the role of of the slow L.D.A. of chicken and has and will certainly prove to be ca++ ions, which have such an im­ of the soleus of rats is increased the most helpful concerning the portant role in the process of exci­ compared with that of the fast problem of basic conceptions of tation-contraction coupling (see L.D.P. of chicken and the E.D.L. contraction mechanisms (see Fis­ Sandow, 1965). It may suffice to of rats (fig. 3). Also a higher level cher, 1944). Hetero-innervation ex­ point out that caffeine increases the of ribonucleic acid content was periments were used to show the capacity of the sarcoplasmatic re­ found (mg RNA/100 mg of pro­ effect of an additional nerve supply ticulum to release Ca++ (see Sandow, teins) in the slow L.D.A. of the on contracture behavior of the 1965) and that ACh increases the chicken, rectus abdominis of the muscle (Gutmann and Hanzlikova, inward movement of Ca++ following frog and soleus of the rat compared to be published) . If the peroneal an increase in membrane permea­ with the fast L.D.P. of the chicken, nerve is sutured into the soleus bility (Jenkinson and Nicholls, sartorius of the frog and E.D.L. of muscle (this is a hetero-innerva­ 1961). Moreover, the sarcoplas­ the rat (Gutmann and Syrovy, tion) and simultaneously the tibial matic reticulum, the structure which 1966, to be published) . These are nerve is crushed, hyperneurotization apparently mediates the process of first indications of a higher turn­ of the soleus muscle due to the ad­ excitation-contraction coupling, is over of proteins of slow muscles, ditional supply of fast peroneal relatively less developed in the slow but, of course, more data will be nerve fibers is achieved. The addi­ (tonic) muscle fibers of the frog necessary to strengthen the assump­ tional nerve supply affects the con­ (see Page, 1965). In analogy, sen­ tion of a relation of speed of pro­ tracture behavior of the reinner­ sitization of the E.D.L. to caffeine teosynthesis and mechanisms con­ vated soleus muscle, apparently by contracture caused by denervation cerned with maintenance of ten­ mediating fast nerve influences. In suggests alterations in the sarco­ sion. these experiments only the tibial plasmatic reticulum and in its ca­ nerve was crushed on the control pacity to regulate the myoplasmic CONCLUSIONS side. Both muscles react with con­ flux of Ca++ (Gutmann and Sandow, tracture to a solution of caffeine. 1965) . On the basis of the clear-cut dif­ Five weeks after reinnervation of Our next consideration concerns ferentiation used in fast (twitch) the muscles, the tension developed the well-known differences of en­ by the contracture was 2.26 ± ergy metabolism of fast ("white") 0.26 g in the control muscles (re­ and slow ("red") muscles. In the 200 innervated by the tibial nerve only) former, anaerobic glycolysis, cat­ and 1.30 ± 0.24 g (10 animals) in alyzed by the enzymes of the Emb­ 150 the muscle reinnervated by tibial den-Meyerhof chain, apparently LDPIEDL. and hyperneurotized by peroneal plays the dominant role; in the lat­ nerve fibers. Thus the additional ter, the oxidative processes cat­ 50 fast nerve influence had reduced alyzed by enzymes of the citric acid the contracture response of the slow cycle (the intramitochondrial en­ L.DA SOLEUS soleus muscle. zymes dominate; see Pette, 1965). These differences are apparently re­ Fig. 3-lncorporation of radioactive S35 methionine into the proteins of the DIFFERENCES IN METABOLISM lated to adaptation to different func­ M. latissimus dorsalis anterior of the tional demands (e.g., Needham, OF "FAST" AND "SLOW" chicken and the M. soleus of rats MAMMALIAN MUSCLE FIBERS 1926; Yakovlev and Yakovleva, (counts/ min/ mg of precipitated pro­ RELATED TO DIFFERENT 1953) and are reflected in the dif­ teins) one hour after intraperitoneal ferences of speed of contraction 35 CONTRACTU RE BEHAVIOR injection of S methionine (200 µcl (Close, 1964). 100 g of body weight). Specific ac­ The differences in contracture However, slow (tonic) fibers of tivity is expressed in percent of activ­ behavior between fast and slow frog, toads, or chickens and slow ity measured in the M. latissimus mammalian muscle fibers suggest mammalian muscle fibers alike are dorsalis posterior of the chicken and that two basic groups of muscle required for posture and mainte­ the M. extensor digitorum longus of fibers may exist, which may be nance of tension for long periods of the rat (white columns). The levels of ribonucleic acid content (see somehow related to the differences time, and differences in protein Schneider, 1945) in L.D.A. of chicken of fast (twitch) and slow (tonic) metabolism of two basic types of and the M. soleus of the rat ('YP/ mg muscle fibers of the frog. Are there muscle fibers related to "long-term protein) are expressed in percent of indications of differences of metab­ regulations" might be expected. This the RNA content in the L.D.P. of the olism between such basic groups of is indeed the case. chicken and in the E.D.L. of the rat muscle fibers? Incorpora tion of radioac- (black columns) .

80 E. GUTMANN and slow (tonic) muscles of the GIN ETZINSKY, A. G. AND N. M. SHA­ K uFFLER, S. W. AND R. W. GERARD. frog, both the fast E .D.L. and the MARINA. Tonomotornyj fenomen v The small-nerve motor system to slow soleus muscle should be con­ denervirovanoj mysce. Usp . Sovr. skeletal muscle. J. Neurophysiol. sidered twitch muscles. However, Biol. 15: 283, 1942. 10: 383-394, 1947. they reveal a marked differential GRAY, E. G. Structures of fast and MILEDI, R. The acetylcholine sensi­ tivity of frog muscle fibres after behavior in their contracture re­ slow muscle fibres in the frog. J. Anal. 92: 559-562, 1958. complete or partial denervation. J. sponses to ACh and caffeine. More­ Physiol. 151 : 1- 23, 1960. over, all the slow muscles I have GUTMANN, E., I. JIRMANOVA, L. VYK­ LICKY. Contracture responses of the MILEDI, R. Junctional and extrajunc­ studied (i.e., the L.D.A. of the latissimus dorsi ant. and post. of tional acetylcholin receptors in chicken, the rectus abdominis of the chicken, to be published. skeletal muscle fibres. J. Physiol. the frog, and the soleus of the rat) G UTMANN, E. AND A. SANDOW. Caf­ 151: 24-30, 1960. show a higher rate of proteosyn­ feine-induced contracture and po­ PAGE, S. G. A comparison of the fine thesis. This may be related to the tentiation of contraction in normal structures of frog slow and twitch basic function of slow muscles con­ and denervated rat muscle. Life muscle fibres. J. Cell Biol. 26 : 477- cerned with long-lasting mainte­ Sci. 4: 1149, 1965. 497, 1965. nance of tension, the extreme being, GUTMANN, E. AND I. SYROVY . Protein PEACHEY, L. D. Structure of the sar­ for example, the contracture re­ metabolism in fast and slow muscle coplasmic reticulum and T system sponses observed in reaction to fibres, to be published. of striated muscle. Proc. Int. Union of Phys. Sci. 4: 388, 1965. ACh. There may be a relation of GUTMANN, E. AND V. HANZLIKOVA. PETTE, D. Plan und Muster in zel­ rate of protein metabolism to the Contracture responses of fast and lufaren Stoffwechsel. Naturwissen­ slow mammalian muscles. Physiol. mobility of protein-bound Ca++ in schaften 52: 597, 1965. Bohemoslov., in press. the sarcoplasmatic reticulum. The NEEDHAM, D. M. Red and white mus­ HEss, A. The structure of slow and differences in contracture behavior cle. Physiol. Rev. 6: 1, 1926. fast extrafusal muscle fibers in the are apparent already three days RIESSER, 0. AND F. RICHTER. Weitere extraocular muscles and their nerve after birth of the animals. All this Beitrage zur Kenntnis der Erre­ endings in guinea pigs. J. Cellular may indicate a basic differentiation gungs-contractur des Froschmuskels. Comp. Physio/. 58 : 63 , 1961. of two main groups of muscle fi­ Arch. Ges. Physiol. (Pfliigers) 207: HODGKIN, A. L. AND P. HOROWICZ. bers. 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