*.bbbb *. * *,,sn. instrumentally and the results to be read as the ballistic deflection. University College, London.)

Transcription

1 THE SUPERNORMAL PHASE IN MUSCULAR CONTRACTION. BY TAKEO KAMADA. (From the Department of Physiology and Biochemistry, University College, London.) 6I THE isometric response of a muscle to a single shock can be measured, not only by the maximum tension developed, but by the area of the tension-time curve. The importance of tension-time is that it is the basis S 3'. <, 25 * ee *e 25 *.bbbb *. * *,,sn 2 : 1 2mi. Ca 15 I"~..1_ Ca loo 5. O Order of twitches Fig. 1. Attainment of steady state during regular series of twitches. Gastrocnemius at C. in 2 Ringer. Horizontally, order of twitch in regular series; vertically, response (tension-time) as galvanometer deflection (mm.). The three series were made in order: 2 min. intervals, 1 min. intervals, i min. intervals. After the first two series a long rest was given. of the maintained contraction: the "economy" of a tetanus depends upon the "area" of a single twitch. The method described below allowe the integration necessary for determining the tension-time to be performed instrumentally and the results to be read as the ballistic deflection of a galvanometer.

2 188 T. KAMADA. Recorded as tension-time the response of a muscle to a single shock shows a striking supernormal phase [Hartree and Hill, 1921] in the sense that at a suitable interval the response to a second shock is greater than that to the first one. Other aspects of this supernormal state have been referred to recently by Hill [1931 a, p. 296] and by Rushton [1932, p. 244]. In the present research its characteristics have been further investigated. o 2 S~~~~~ o o o OO A. 15B Order of twitches Fig. 2. Change in steady state due to change of interval between twitches. Gastrocnemius at C. in 2 Ringer. Horizontally, order of twitch in regular series; vertically, response (tension-time) as galvanometer deflection (mm.). The series with 2 min. intervals (solid circles) occurred first. After the. establishment of a steady state (level B) the interval was diminished to 1 min. (double circles). When the new steady state (level A) was established the interval was changed back to 2 min. and a third steady state was found at the same level B as before (solid circles). After about one hour's rest the muscle was stimulated again in a regular series at 1 min. intervals (hollow circles); the steady state was now reached at level A. If a regular series of shocks be given to a muscle at not too high a rate the tension-time response (hereafter referred to as the response) increases until it reaches (apart from the onset of fatigue) a stationary level (see Fig. 1). Increasing the interval then causes a fall, decreasing the interval a rise in the level (see Fig. 2). If at any moment after one of the shocks of such a series an extra shock be interpolated, the response is greater or less according to the relations described below.

3 SUPERNORMAL PHASE IN CONTRACTION. 189 METHOD. A differential cuprous oxide photoelectric cell was employed, as suggested by Hill [1931 b]. It was joined to a slow sensitive moving coil galvanometer employed ballistically. The gastrocnemius of a small Dutch frog (R. esc.) was connected by a wire to an isometric spring myograph, from the mirror of which a strong beam of light was reflected on to the middle of the cell. When the muscle contracted, the beam of light moved and generated a current in the cell. The amount of current so generated and recorded by the galvanometer was proportional to the tension-time. The muscle was stimulated by single super-maximal induction shocks through its nerve. Two Harvard coils placed at right angles on the table were adjusted to give identical shocks, their secondaries being arranged in series with the electrodes. The time interval was regulated by a Lucas revolving contact breaker, with one key in the primary of each coil. When many successive shocks were given the cam contact breaker described by Gerard, Hill and Zotterman [1927] was used with a single coil. The preparation was immersed in phosphate Ringer's solution (ph 7.2), oxygen or nitrogen being passed continuously. RESULTS. When a muscle was stimulated at regular intervals with single shocks, the response increased gradually to a constant value (Fig. 1). During this " steady state " the response depends on the interval between shocks, being greater with shorter intervals. Usually the steady state was stable, except in the absence of oxygen, when fatigue set in. The supernormal phase was tested after the establishment of the steady state by interpolating an extra shock. The muscle then had to contract twice in one interval, so that the next regular shock gave a slightly greater response. Continuing, however, with the regular series the steady condition was re-established. Following this routine, the supernormal effect at the second of two stimuli was determined with various intervals. Two different stages are found: (a) the relatively refractory phase, in which the second response is less than the first; (b) the supernormal phase, lasting up to the next regular shock, in which the second response is the greater. A third, but artificial, subnormal phase is then found in which, owing to the necessary omission of the next regular shock if an interval greater than that of the series is to be employed, the response is less than in the series.

4 19 T. KAMADA. TABLE I. Gastrocnemius at C. in 2 Ringer: regular series at 1 min. intervals. The supernormal value was obtained by subtracting double the regular response from the summated response (or when possible the regular response from that to the interpolated shock). With intervals more than 2 sec. the galvanometer was short-circuited during the first response: then the short-circuit was opened, so as to obtain the second response only. Interval between shocks (sec.): Supernormal effect (p.c.): When, during a regular series of shocks, a single one is replaced by a group in rapid succession, the extra activity disturbs the steady state and the next response in the regular series is enhanced. TABLE II. Gastrocnemius at C. in 2 Ringer: regular series at 1 min. intervals. Excess of response at next regular shock as the result of extra activity immediately following a shock of the regular series. (Extra activity represented by number of extra shocks at -5 sec. intervals.) Extra shocks Excess response (p.c.) The supernormal phase following a single shock can clearly be regarded as the first step in the establishment of a new steady state. This is true even of as short an interval as *5 sec. at 9 C. In such a case each shock is applied during and not after the previous contraction, and the total effect of a group of shocks must be read as a whole. With the longer groups the galvanometer had to be employed beyond the range of its ballistic proportionality, and a correction was employed by means of an experimental curve relating deflection to duration of illumination TABLE III. Gastrocnemius at 9.4 C. in 2 Ringer: regular series at 1 min. intervals. No. of Mean super- Sequence of extra shocks normal effect of observations -5 sec. extra shocks Average A, apart p.c. p.c ~~

5 SUPERNORMAL PHASE IN CONTRACTION. 191 of the photoelectric cell by an unsymmetrical light spot. See Fig. 3 and Table III. At higher temperatures the phenomena of the supernormal phase are not so evident, and the time intervals at which they must be sought are much less. At 2 C., for example, an interval of 5 sec. should correspond approximately to one of 1 min. at C. In the paper by Hill [1931 a, Fig. 9, p. 296] there are obvious supernormal responses to the later shocks of a *9 sec. and a -6 sec. series at 2.2 C. Since the i Extra shocks Fig. 3. Constructed from Table III. Horizontally, number of extra shocks at 5 sec. intervals given immediately after one of a regular series of shocks at 1 min. intervals; vertically, mean supernormal effect, i.e. mean response of extra shocks in excess of response in regular series expressed as a percentage of the latter. Gastrocnemius at 9.4 C. in 2 Ringer. intervals required are longer and the phenomena are more evident at the lower temperature, attention in the present research has been directed chiefly to these. DIsCUSSION. It has been shown that the tension-time response is greater, after a short interval during which it is less, the less complete the return of the muscle is to its resting or steady condition at the moment of response. There are two factors in this increase of the area of the tension-time curve, namely the usual staircase effect and the "slowing " effect recently referred to by Hill [1931 a, Fig. 9]. The latter factor seems to be much the more important. The supernormal phase in the thermal response and that in the mechanical response are independent of each other [see Hartree and Hill, 1921, Fig. 6]. There are various other forms of response in which a supernormal phase has been reported, e.g. in the electric response

6 192 T. KAMADA. [Samo jioff, 198; Adrian and Lucas, 1912], in the height of isotonic contraction under certain conditions [Bremer and Homes, 1932] and in the return of excitability [Adrian and Lucas, 1912; Cooper, 1924]. Whether there is any connection between the various supernormal phenomena is not certain. SUMMARY. If a regular series of single shocks be given to a gastrocnemius muscle through its nerve its tension-time response increases until a stationary level is attained. Increasing the stimulation interval causes a fall, decreasing the interval a rise in the level, so far as this is not affected by the onset of fatigue or by the relatively refractory period. The so-called supernormal response, at least in the case of the tensiontime of a contraction, can be regarded as the first step towards a change in the steady level due to a sudden change of the stimulation interval. I am deeply indebted to Prof. A. V. Hill who suggested the method, and under whose kind direction and help the work was carried out. To Mr J. L. Parkinson I wish to express my thanks for his assistance in the technique. REFERENCES. Adrian, E. D. and Lucas, K. (1912). J. Physiol. 44, 68. Bremer, F. and Hombs, G. (1932). Arch. int. Physiol. 35, 39. Cooper, S. (1924). J. Physiol. 59, 82. Gerard, R. W., Hill, A. V. and Zotterman, Y. (1927). Ibid. 63, 13. Hartree, W. and Hill, A. V. (1921). Ibid. 55, 389. Hill, A. V. (1931 a). Proc. Roy. Soc. B, 19, 294. Hill, A. V. (1931 b). J. Sci. Instr. 8, 262. Ruslhton, W. A. H. (1932). J. Physiol. 74, 231. Samojloff, A. (198). Arch. Anat. Physiol. Leipzig, Suppl. p. 1.