ABSTRACT The ability of limpets to exhibit high tenacity in clamping down on rocks for prolonged periods of time is accounted for by a possible catch mechanism. Contractile properties of a preparation of the shell-foot retractor muscle of the limpet Lottia gigantea were investigated using salines of altered ionic concentrations and known muscle effectors (caffeine, acetylcholine, and 5-hydroxy- tryptamine). The following results were obtained; 1. The shell-foot retractor muscle exhibits twitch responses and summation characteristic of most muscle types. 2. Acetylcholine, caffeine, high K'saline and high K- caffeine saline induce muscle stress in the absence of electrical stimulation. 3. 5-HT reduces muscle stress in the absence of electrical stimulation. 4. High Ca, low Na, caffeine, high K, high K-caffeine, a hypertonic solution, Ach and 5-HT potentiate a contraction in response to electrical stimulation. The responses vary between test salines and depend on prior response to electrical stimulation and exposure time of 'the muscle to the test solution. 5. Acetylcholine alone induces a sustained contraction stress. 5-HT relaxes this contraction at a relaxation rate 33 times the rate in acetylcholine alone. This pharmacologic response is evident in muscles known to exhibit a catch mechanism of contraction. A maximum contraction stress of 3.1x 10° N/m was measured in the shell-foot retractor muscle. To obtain an indication of the muscle contribution to limpet tenacity this value was compared to the stress necessary to dislodge a tightly clamped limpet from an intertidal rock and found to be of equal magnitude. INTRODUCTION Molluscan muscle has the capability to develop great tensions and sustain prolonged contraction stresses through a "catch" mechanism. This mechanism has been extensively studied in the anterior byssus retractor muscle (ABRM) of Mytilus edulis (Twarog 1954,1960,1967,1967a, 1968. 1969,1971,1972) and it is believed to be a type of mechanism available to many muscles which may develop specialization for catch to varying degrees (Wilson and Larimer 1968). I examined the possibility that a catch mechanism exists in limpet shell-foot retractor muscle. The existence of such a mechanism might account for limpets' ability to remain tightly clamped down on a rock for extended periods of time when faced with wave shock or dessication stresses. This work is the first to study the properties of limpet muscle. I began by examining the muscle response to single and repeated electrical stimulation of varying strength, duration, and frequency. Interest in the catch hypothesis then led me to examine the pharmacological properties of the muscle. By altering a standard artificial seawater solution, the effects of relative concentrations of major ions were tested on the muscle, using the solution alone and accompanied by electrical stimulation; changes in the contraction stress and relaxation times were noted, Known muscle effectors such as caffeine, acetylcholine and 5-HT salines were also used to examine contractile properties of the muscle preparation. Data suggestive of catch is discussed as are effects of certain test salines on the muscle contraction stress. MATERIALS AND METHODS Lottia gigantea were collected at Pacific Grove, Ca.. and kept at 14 degrees Celsius in circulating seawater. Limpets were injected with 5 ml MgCl, solution (1 part I M MgCl, to 2 part seawater) to induce relaxation in the foot muscle. With the limpet on its dorsal side, longitudinal cuts 5mm apart were made on the shell-foot retractor muscle from its point of attachment on the shell to the ventral surface of the foot (10-12 mm depending on the size of the limpet). The muscle segment was then teased away from the shell and the most lateral layer (lmm) was used as the final preparation (dimensions: 10mmx 5mmx lmm). The muscle preparation was placed in running seawater for 1 hour to allow recovery from the anesthetic. The preparation was mounted horizontally between two flattened alligator clips. One clip was fixed to the bottom of the dish containing the test solution. A force transducer was attached via a fine chain to the free-moving clip, The sample was stretched by approximately 202 (2mm) above its dissected length to return it to its in vivo length (as measured in the intact limpet prior to dissection). This extension required a force of 0.2 N(a stress of 4 x 10" N/m*). An additional loading force of O.25N was applied (total loading stress of 9x 10' N/m. A Grass S44 stimulator and a bipolar electrode were used to deliver electrical stimuli to the muscle. A standard artificial seawater solution (ASW) was used as a control (470 mM Nacl, 10 mM KCl, 10 mM Cacl,, 5 mM Hepes, pH - 8.1) to test the following altered salines: High K (400mM KCl, 80 mM Nacl), caffeine (30mM), high K-caffeine (30 mM in high K), high Ca (replaced Mgcl with Cacl.), low Na(replaced NaCl with Triscl), 5-hydroxytryptamine (10-4M). acetylcholine (10 "M) and a hypertonic solution (300mM in ASW). All solutions were titrated to pH of 8.1 with .5M Naoh and stored at 4 degrees Celsius. Experiment 1 Single and twin shocks of 12 Volts, 50 millisecond pulse duration were applied to muscle preparations in ASW. The interval between double stimuli was varied between 2 and 10 seconds. Experiment 2 The rate of repeated stimulation was varied from 1 to 10 pulses per second at 15 Volts, 60 ms pulse duration for 33 second applications. Experiment 3 The effect of various solutions on the stress developed by the muscle were investigated. Each solution was tested on 8 muscle samples. Each muscle sample was used to test only one solution and its ASW control. Solution baths were maintained at 15 degrees Celsius and were flushed every 10 minutes (except when indicated) in the following order: ASW, test solution, ASW, test solution. The effect of the solution alone on the muscle was tested without elec- trically stimulating the muscle in the bath. Eight muscle samples were then bathed in each solution and this time the muscle was electrically stimulated. Series of shocks of 90 Volts, 6 ms pulse duration, 10 pulses per second, and 3 second duration were applied. At the time of maximum tension evoked by the solution alone, the first series of shocks was applied; a second series was applied 1 minute later, etc. In solutions in which there was no measurable effect on the muscle stress by the solution alone, the first series of shocks were delivered after 2 minutes of bathing and the second series after 3 minutes, etc. Contraction stress, contraction times (time from baseline to maximum peak) and relaxation times (time from peak to baseline) were calculated for each muscle response. Experiment 4 Repeated single shocks of 60 Volts, 6 ms pulse duration with 10 second intervals between shocks were applied to 8 muscle samples in contact with (but not submerged in) ASW. High K-caffeine (5ml) saline was applied directly onto the muscle while it was still in contact with ASW. Experiment 5 Three muscle preparations were placed in contact with Ach saline and allowed to remain there until the muscle stress subsided to baseline. 5-HT (5ml) was applied directly to the muscle once the maximum muscle stress evoked by the Ach solution was reached. (elaxation times for Ach alone and Ach + 5-HT trials were recorded. RESULTS Experiment 1: A single contraction was evoked by a single stimulus and is therefore classified as a twitch response. Based on criteria in Schmidt-Nielsen (1979) the waveform obtained in the response is characterized as phasic (Figure 1) Double stimuli set apart by short intervals result in summation and a contraction stress higher than that evoked by a single twith is recorded. Experiment 2: Repeated stimulation of the muscle at 15 Volts and 60 ms pulse duration, 1 pps, and 33 second duration evokes a tonic waveform. Summation in the tonic mode at a rate of I pps gives a characteristic "sawtooth" appearance. A higher rate of stimulation (10 pps) evokes a higher maximum stress and fusion to a tetanus (Figure 2). The responses recorded in the first two experiments are characteristic of most muscle types (Mattison and Arvidsson 1966; Heyer et al 1973; Schmidt-Nielsen 1979). Experiment 3: Figure 3 shows those solutions which by themselves affected the muscle stress. Also indicated are the additional effects of the first series of electrical stimuli in the given solution. The hypertonic solution, high Ca and low Na salines alone had no measurable effect on the muscle stress and therefore are not included in Fig.3. Figure 4 shows the effects of the first and second series of shocks on the muscle stress in each test solution expressed as a percentage increase above the stress measured in Asw (12 x 10" N/m2 in the first series and 11.4 x 104 N/m in second series of shocks). High Caf: The high Ca saline potentiated a contraction stress when the muscle was electrically stimulated. Stresses evoked by the fourth series of shocks were equal to those evoked by the second series of shocks. This finding is contrasted with that in ASW after the fourth series of shocks, where the stresses were half the size of those evoked by the second series of shocks in ASW. Low Na: Low Na saline potentiated a contraction appro- ximately 367 above that of ASW in the first series of shocks. However, note that the response to the second series of shocks in the solution shows a great decrease from the first contraction stress. Hypertonic saline solution: After a 5-minute bath in hypertonic saline, the muscle responded to electrical stimulation with a contraction stress higher than that in ASW. In contrast to this, a 1-hour bath in hypertonic saline depressed the muscle response to electrical stimulation to a stress 452 below that in ASW. Caffeine: Although caffeine itself had minimal effect on the muscle, it appears to potentiate the highest contraction stress of all the solutions tested in response to electrical stimulation. The response can be repeated provided that a rest interval of 60 seconds is allowed between trials. However, after six repetitions, the contraction stress evoked became successively lower (2 x 10' N/m' after six series of shocks) than would be accounted for by fatigue (as measured in ASW (6 x 10* N/m2). Note that these values are those obtained by the applied stimulus and do not include the loading stress of 9 x 10* N/m?. High K and High K-caffeine: High K and High K-caffeine salines potentiated tonic contractions which peaked at 40 seconds and 30 seconds respectively after the initial contact with the muscle. The muscle responsiveness to electrical stimuli in the High Kalone decreased to zero after the first 4 minutes in the bath. When caffeine is present in the high K medium however, the muscle remains responsive to electrical stimulation for the first 7 minutes of bathing. The relaxation time after a shock in High K alone is decreased from 27 seconds to 8 seconds when caffeine is in the medium (Figure 5). The relaxation time of the phasic waveform after electrical stimulation in the caffeine saline alone is approximately 6 seconds. Note that when both high K and caffeine are in the same medium, the rela¬ xation time is not an average of the two but is much closer to that measured in caffeine alone. Figure 5 illustrates typical waveforms in caffeine, high K and high K-caffeine. Experiment 4: Figure 6 illustrates the summation effect of repeated single shocks of 60 Volts, 6 ms pulse duration, 10 second intervals between shocks. Note that the stress does not increase on every consecutive shock but instead there is a tendency to maintain a constant stress (first 10 shocks). When high K-caffeine is added directly onto the muscle, the stress increases on each subsequent shock (shocks + 10-15) until it reaches a maximum. This stress decreases despite continued stimulation. The addition of high K-caffeine during this stress decrease appears to prevent further loss of stress and even enhances the response of the muscle to continued electrical stimulation. I can offer no specific mechanism for this action of high K caffeine. Experiment 5: Although Ach (10 *) itself had minimal effect on the muscle, it potentiated a contraction stress of 25 x 10' N/m' when the muscle was electrically stimulated in the solution (from Experiment 3). The second series of shocks in Ach evokes a stress equal to that evoked by the second series in ASW (20.4 x 10' N/m2). When the muscle was exposed to 5-HT (10 M) alone, a 1002 relaxation of the loading stress (9 x 10' N/m2) was observed. When electrically stimulated, muscle in 5-HT was more responsive than the same muscle in ASW. This is reflected in the absolute increase in stress caused by the 5-HT saline after electrical stimulation (18 x 10' N/m) of the muscle. Compare this with an absolute increase in stress in ASW in response to equivalent electrical stimulation (12 x 10“ N/m2). However. because the shock in 5-HT was applied at an already decreasing stress of 3 x 10' N/m2 (Figure 3). Figure 7 illustrates the sustained contraction stress in response to Ach and the relaxing effect induced by 5-HT. Ach potentiated the muscle to sustain a stress of lX 10' N/m' for 420 seconds in the absence of electrical stimulation. a relaxation rate of 23.8 N m2/sec. The application of 3-HT at the point of maximum contraction stress (possible catch state) evoked by Ach alone causes a relaxation to baseline in 25 seconds, a relaxation rate of 800 N m-2/sec. approximately 33 times faster than the rate in Ach saline alone. DISCUSSION The characteristic sawtooth appearance that fuses to a tetanus at higher rates of repeated stimulation is also observed in Cryptochiton stelleri (Harrison 1975). By adjusting the frequency of stimulation above the minimum for tetanus, a several fold increase in the stress is possible. This is in contrast to most vertebrate muscle (cat eye muscle being an exception) where variation in stimulation frequency has little influence on force. Note that the degree to which a given test saline alone potentiates a contraction varied widely between solution and further differed when an electrical stimuli was applied to the muscle in the bath. The mechanism of potentiation of contraction is not clearly understood but it is likely to involve many sites of action (Schulman and Weight 1976). The data generated in this work cannot elucidate the details of the potentiation mechanism but does suggest some general aspects likely to be involved in the overall mechanism which will be discussed in different sections. High Ca Direct entry and diffusion of Ca through the small diameter of the shell-foot retractor muscle cells more than likely accounts for muscle contraction as is found for other molluscan muscles (Huddart et al 1977, retractor and columella muscles). In experiment 3 the ability of the muscle to repeatedly develop a constant muscle stress (equal to that developed after the second series of shocks) in response to a fourth series of shocks is suggestive of the importance of an external Ca concentration. This response may have been possible only in the presence of the high Ca "of the saline. Fatigue seems to have been significantly lowered from that observed in ASW after the fourth series of shocks. The external Ca may have shifted the ionic balance at the cell membrane in favor of repeated potentiation of contractions of constant stress. Since the high Ca levels potentiated a contraction 257 higher than in AsW after the first series of shocks(Figure 4). it could be said that the rate of entry of Ca into the cell is likely to be fast enough to enable potentiation in response to this specific electrical stimulation. If the rate is faster than the rate required to potentiate in response to repeated stimuli, it may account for potentiation of twitches as well (as in skeletal smooth muscle). However. if the rate of entry is not fast enough for twitch potentiation then the Ca" concentration may only play a role in prolonged contractions evoked by repeated stimuli. Atwater (1974) found evidence for the latter in the giant retractor cells of Megabalanus psittacus. Low Na Note that the low Na saline I used is actually a zero-Nat saline (Triscl replacement). Therefore, the inability of the muscle to develop a substantial stress on the second series of shocks in this low Na (302 decrease below the stress developed in ASW) suggest the need to have an external Na concentration to allow responses to electrical stimulation beyond the initial series of shocks. Subsequent responses may need a Na influx such as that required in vertebrate skeletal muscle to initiate an action potential and cause a contraction. Enough Na may have already been present in the immediate surroundings of the muscle cells to allow a subs- tantial response to the first series of shocks in the low Na saline. Experiments with high Na saline and blocking agents such as curare might elucidate the nature of the mechanism involving Nakions (i.e. the possible existence of a sodium pump). Hypertonic Saline The performance of the muscle after a 5-minute bath in hypertonic saline compared with its performance after a 1-hour bath in hypertonic saline indicates a loss of responsiveness to electrical stimulation possibly due to prolonged exposures to high tonicty (Figure 4). This response may be experienced in vivo when the limpet is challenged with osmotic stresses and/or dessication. After the first two series of shocks, progressive series of stimuli for an hour thereafter however, evoked constant stress never below 50% of the corresponding stress in ASW. This data indicates that although the stress evoked in hypertonic saline is far from maximum, it does not change sharply over time after the first hour of exposure to hypertonic media. It would then be fair to expect that a live limpet should be able to withstand prolonged periods of conditions which cause its muscle to be in a hypertonic state, despite its overall depressed ability to evoke high contraction stress. Its tenacity might be expected to be lower due to a depressed muscle performance; however. the rate at which its tenacity decreases will likely remain relatively constant over time. Caffeine Caffeine has been reported to modify the properties of sarcotubular preparations (Weber and Herz 1968). surface membrane of muscle (Bianchi 1961) and nerve terminals (Hofmann 1969). The common denominator for these different manifestations is an effect of caffeine that induces changes in the distribution of Ca and modifies its movement across cellular membrane components. Mechanisms evident in muscles that respond to caffeine in the same way that the shell-foot retractor muscle does suggest a Ca mobi- lization role for caffeine. It is credited with increasing the cell membrane permeability to Ca'tinflux and efflux. (Sandow 1965, frog semitendinosus; Muneoka and Mizonishi 1969, Nytilus edulis; Chiarandini 1970, crayfish; Ashley 1977. Blanus nubilus). The results obtained in experiment 3 showing the successive decrease in stress after the sixth series of shocks (a stress reduction lower than can be accounted for by fatigue) in the caffeine saline may suggest that the source from which caffeine releases Ca' to induce contraction is dependent at least in part on the external Ca concentration. A similar result in response to caffeine was found in crayfish muscle (Chiarandini 1970). It would be interesting to treat the SFR muscle with high Ca'and low Ca2 salines to test for any differences in repeated response to electrical stimulation. High Kand High K-Caffeine The unresponsiveness of the muscle in the High Kafter 4 minutes of bathing and electrical stimulation may be an indication that the high K increasingly depolarizes more of the muscle cell membranes over time, thus rendering it virtually impossible to evoke a further mechanical response when the muscle is shocked. The shortened relaxation time of a contraction in high K-caffeine (Figure 5) seems to suggest that the depolarizing action of high kon the cell membrane is either slowed down or somewhat counteracted by the action of caffeine on the muscle. Axelsson and Thesleff (1958) found the same result in vertebrate striated muscle. A mechanism for this effect cannot be derived from the data I obtained. Acetylcholine and 5-HT Potentiation of contractions by Ach in response to electrical stimuli and the relaxation caused by 5-HT alone on the shell-foot retractor muscle have also been found in gastropod radular retractor muscles (Mattison and Arvidsson 1966). The enhanced response to electrical stimulation in 5-HT (concentrations below 10 6M) were also found in other gastropods (Kobayashi and Muneoka 1980) and in an opistobranch (Cohen et al 1978). The increase in relaxation rate caused by S-Hr on Ach-induced stress is suggestive of a catch mechanism. as is found in the ABRM of Mytilus edulis. Ach injections (10 M) in the isolated ABRM initiate catch (Cole and Twarog 1971) and 5-HT(10"M), the probable transmitter substance feleased by relaxing nerves in Mytilus (Twarog 1954,1968) release catch. Certain features of its mode of action are known (Cole and Twarog 1971) while other remain unclear. Some evidence points to its effect in increasing membrane conductance and triggering reaction cascaded to reduce the level of free intracellular Ca tTwarog 1966), an effect opposite that of caffeine. It may be worthwhile to conduct an experiment to test the effect of 5-HT applications on a muscle previously bathed in caffeine. Table 1(adapted from Schmidt-Nielsen 1979) gives maximum contraction stress values measured in various animals. I measured a value of 3.1 x 102 N/m2 for the limpet shell- foot retractor muscle. This stress was reproducible as it did not irreversibly damage the muscle preparation. To get an indication of the contribution the muscle contraction stress makes to a limpet's tenacity, this value can be compared to the stress necessary to pry a limpet off a rock. The latter is a value of 1-4 x 10° N/m? (Denny 1985 pers.comm) and it is created by a low pressure in the mucus of the foot when the retractor muscle contracts, thus adhering the limpet to the rock and accounting for its high tenacity. My value may be an underestimate due to the nature of the muscle preparation in which it was measured. I did not work with individual muscle fibers; therefore, the number of fibers contracting in any one particular direction upon stimulation, is likely a function of their angle of orientation relative to the direction in which the contraction stress is measured. Nevertheless, if one assumes that the limpet is exerting maximum contraction stress when it detects a stimulus on its shell to avoid being dislodged, then this value of 3.1x 10° N/m reflects the ability of the SFR muscle to account for most of the stress necessary to keep the limpet clamped down on the rock. Factors such as osmotic stress and/or dessication may also play an interactive role in affecting the limpet's tenacity (Boggs and Marzuola, pers. comm). LITERATURE CITED Ashley, C., Ellory, J.C., and Griffiths, P.J. (1977). Caffeine and the contractility of single muscle fibres from the barnacle Balanus nubilus. J. Physiol., 269,421-439. Atwater, I., Rojas, E., and Vergara, J. (1974). Calcium influxes and tension development in perfused single barnacle muscle fibers under membrane potential control. J. Physiol., 243, 523-551. Axelsson, J., and Thesleff, S.(1959). A study of super- sensitivity in denervated mammalian skeletal muscle. J. Physiol., 149,178-193. Bianchi (1961). The effects of caffeine on radiocalcium movement in frog sartorius., J. Gen. Physiol., 44, 845-850. Chiarandini, D.j., Reuben, J.P., Brandt, P.W., and Grundfest, H. (1970). Effects of caffeine on crayfish muscle fibers. J. Gen. Physiol., 55, 640-662. Cohen, J.L., Weiss, K.R., and Kupferman, I.(1978). Motor control of buccal muscles in Aplysia. J. Neurophysiol., 41,157-180. Cole, R.A., Twarog, B.M. (1972). Relaxation of catch in a molluscan smooth muscle. Comp. Bioch. Physiol. 43, 321-330. Harrison, J. T. (1975). Isometric responses of the somatic musculature of Cryptochiton stelleri. Veliger 18 (Suppl), 79-82. Heyer, C.B., Kater, S.B., and Karlsson, U.L.(1973). Neuro- muscular systems in molluscs. Am. Zool., 13, 247-270. Hofmann, A. (1969). Caffeine effects on transmitter depletion and mobilization at motor nerve terminals. Amer. J. Physiol 216, 621-630. Royle, G. (1983). Nuscles and their neural control. Nev York: John Wiley and Sons, Inc., 689 pp. Auddart, M., Hunt,S., and Oates, K. (1977). Calcium movements during contraction in molluscan smooth muscle, and the loci of calcium binding and release. J. Exp. Biol. 68, 45-56. Kobayashi, M., and Muneoka, Y. (1980). Modulatory actions of octopamine and serotonin on the contraction of buccal muscles in Rapana thomasiana. I. Enhancement of contraction in the radula protractor. Comp. Bioch Physiol., 650,73-79. Mattison, A.G.M., and Arvidsson, J.A.(1966). Some effects of electrical stimulation and exogenous metabolites on the contractile activity and the ultrastructure of the radula muscle of Buccinum undatum, 2. Zellforsch, 73,37-55. Muneoka, Y., and Mizonishi, T. (1969). Effects of changes in external calcium concentration on the caffeine contracture of ABRN of Mytilus edulis. 20ol. Magazine 78, 101-107. Sandow, A. (1965). Excitation-contraction coupling in skeletal muscle. Pharm. Rev. 17, 265-320. Schmidt-Nielsen, J.A., and Weight, F.F. (1976), Synaptic transmission: long-lasting potentiation by a post-synaptig mechanism. Science 194,1437-1439. Iwarog, B.M. (1954). Responses of a molluscan smooth muscle to acetylcholine and 5-hydroxytryptamine. J. Cell Comp. Physiol. 44, 141-164. Twarog, B.M. (1960). Innervation and activity of a molluscan smooth muscle. J. Physiol. 152,220-235. Iwarog, B.M. (1967). Excitation of Nytilus smooth muscle. J. Physiol. 192,857-868. Twarog, B.M. (1967a). The regulation of catch in molluscan muscle. J. Gen Physiol. 50, 157-169. Twarog, B.M. (1968). Possible mechanism of action of serotonin on molluscan muscle. Adv. Pharmac. 6, 5-15. Twarog, B.M., and Hidaka, T.(1971). The calcium spike in Mytilus muscle and the action of serotonin. J. Gen. Physid 57, 252. Weber, A. and Herz, R. (1968). The relationship between the caffeine contracture of intact muscle and the effect of caffeine on reticulum. J. Gen. Physiol. 52,750-762. ACKNOWLEDGEMENTS I thank Hopkins Marine Station for being the great research facility that it is and for complementing my Stanford education with unforgettable memories. Very speci thanks go to my advisors Dr. Mark Denny and Dr. William Gilly for their guidance and dedicated instruction as well as to Stuart Thompson for constructive criticism of this work. To my fiancee Keith Tansey for his patience and love throughout our Hopkins' days and for a lifetime ahead FIGURE 1. FIGURE 2. FIGURE 3. FIGURE 4. FIGURE LEGENDS Twitch response to single and double stimuli. The interval between double stimuli is increased from 2 to 10 seconds. Summation and Tetanic Response. Increasing the frequency of repeated stimulation from 1 pulse per second to 10 pulses per second causes fusion to a tetanus. Effects of Solutions and Electrical Stimulation on the Contraction Stress of the Muscle. The effect of each solution alone is indicated by the cross-bars. Additional effects of the first series of shocks in each solution are indicated by the clear bars. Effect of Series of Shocks on Muscle Contraction, Responses are expressed as net percentage increases above (or decreases below) the muscle stress evoked in artificial seawater (ASW), 12 x 10' N/m? and does not include the loading stress of 9 x 104 N/m2 which was common to all the muscle preparations. The second series of shocks in the test solutions are shown'as percentage increases (or decreases) over the corresponding value in ASW of 11 x 10' N/m2. The three percentages slightly above the ASW baseline are in actuality on the baseline denoting a 0% increase. FIGURE 5. Effect of Caffeine, High K and High Ktcaffeine on Waveforms and Relaxation Times. FIGURE 6. Effect of High K-Caffeine on Summation of repeated single shocks. High K-Caffeine potentiates stress accumulation in response to electrical stimulation. It also interferes with decrease of muscle stress in the second application and potentiates subsequent response to electrical stimuli. FIGURE 5-Hr Relaxation of Ach-induced contraction stress. Ach (10""M) bath alone induces a prolonged contraction (top waveform) that can be relaxed by 5-HT (10 "M) at a rate 33 times faster than in Ach. TABLE 1. (Adapted from Schmidt-Nielsen 1979). Contraction Stresses of Various animal muscles. The shell- foot retractor muscle appears to have a maximum contraction stress in the lower range of values listed. 0 6 FIGURE 1 2 Volts 50 ms Twin Shocks 2 sec delay 2.5 sec delay 5 sec delay O4 1O sec delay O1 — 20 25 30 10 15 Time (sec) at- O Qu/NO)s —-- - 1 8 Q 33 30 27 24. 821 o 18. 15. 12 9. 6 3 FIGURE 3. ASW 5-HT L Caffeine High K¬ Caffeine High K Ach AoadingTens Solution alone Solution shock )( )0 1 — — 2 X oo Au o S I O OO (/N)ssa 3 S 4 S u/NOI) s1 1 + 18 18 1 uN) s 0 TABLE 1. ANIMAL Annelid (Arenicola) Limpet (Lottia gigantea) Bivalve (Anodonta) Bivalve (Mytilus) Octopus Insect (Locusta) Insect (Decticus) Insect (Drosophila) Frog (Rana) Rabbit Man MUSCLE Body wall Shell-foot retractor Adductor Anterior byssus retractor Eunnel retractor Hindlegs Flexor tibiae Wing muscles Anterior tibial "Skeletal muscle' Ankle flexors CONTRACTION STRESS (N/m2) 3. 5 4.5 5. 4.7 5.9 5 4.4 5.0 4.2 2