1225
by conventional tissue-culture techbut several different viral agents have been niques, detected by electron microscopy in the fxces of affected people. This technique has proved useful in the investigation of gastroenteritis associated with seafood,2.3 and the latest instance was a very large outbreak in Australia associated with oysters. At least two thousand people were affected and the Norwalk virus was implicated.4 Norwalk was the first virus from human cases of NBGE to be seen electron microscopically.5 Unlike the rotavirus, which is mainly an infection of young children, Norwalk more often infects older children and adults and is believed by some to be a major cause of NBGE. Greenberg and co-workers, in the United States, judged that eight out of twenty-five outbreaks investigated were serologically associated with the Norwalk virus. Outbreaks associated with Norwalk virus are now being investigated in Britain. The mode of transmission is not clear; there have been reports indicating waterborne infectionbut the outbreak in Australia is the first in which infection has been shown to be foodborne. Norwalk is a small round virus of diameter around 27-32 nm; its density and other physicochemical properties suggest that it may belong to the parvovirus group,8 but this classification has not yet been confirmed by identification of the nucleic acid. In several specimens examined from the oyster-associated outbreak a second smaller virus particle, 22-25 nm in diameter, was observed. These particles are similar to those found in the cockle-associated gastroenteritis in England three years ago2 and similar particles have been observed in other outbreaks of NBGE, or "winter vomiting disease", where no food could be implicated.9-11 The particles retrieved in these outbreaks, although morphologically similar, seem to fall into four groups which are antigenically distinct from each other and also from the Norwalk virus. In both the Australian oyster-associated outbreak and the English cockle outbreak the apparent aetiological agents were not found in the shellfish themselves, although one batch of oysters contained the smaller 22-25 nm particle. Oysters and cockles, in common with all bivalve molluscs, can concentrate virus from polluted waters12 but the number of particles present in the shellcannot be grown
2.
Appleton H, Pereira MS. A possible virus aetiology in outbreaks of food poisoning from cockles. Lancet 1977; i: 780-81. 3. Murphy AM, Grohmann GS, Christopher PJ, Lopez WA, Millsom RH. Oyster food poisoning. Med J Aust 1978; ii: 439. 4. Murphy AM, Grohmann GS, Christopher PJ, Lopez WA, Davey GR, Millsom RH. An Australia-wide outbreak of gastroenteritis from oysters caused by Norwalk virus. Med J Aust 1979; ii: 329-33. 5. Kapikian AZ, Wyatt RG, Dolin R, Thornhill TS, Kalica AR, Chanock RM. Visualisation by immune electron microscopy of a 27 nm particle associated with acute infectious nonbacterial gastroenteritis. J Virol 1972; 10: 1075-81. 6. Greenberg HB, Valdesuso J, Yolken RH, et al. Role of Norwalk virus in outbreaks of nonbacterial gastroenteritis. J Infect Dis 1979; 139: 564-68. 7. Center for Disease Control. Morbid Mortal Weekly Rep 1978; 27: 403-04. 8. Kapikian AZ, Gerin JL, Wyatt RG, Thornhill TS, Chanock RM. Density in caesium chloride of the 27 nm "8F 11a" particle associated with acute infectious nonbacterial gastroenteritis: determination by ultracentrifugation and immune electron microscopy. Proc Soc Exp Biol Med 1973; 142: 874-77. 9. Thornhill TS, Wyatt RG, Kalica AR, Dolin R, Chanock RM, Kapikian AZ. Detection by immune electron microscopy of 26 to 27 nm virus-like particles associated with two family outbreaks of gastroenteritis. J Infect Dis
probably remains too low for detection by electron microscopy. In the Australian study an antibody response was detected only to the larger 27-30 nm particle, and the smaller 22-25 nm particle was believed to be unimportant (possibly even a bacteriophage). fish
However, it should be remembered that similar small
particles have been implicated in other outbreaks of NBGE in man and are known to have an important role in gastroenteritis of cattle, cats, and dogs. The presence of virus in faecal samples does not clinch the setiology since symptomless excretion is not unusual with gastroenteritis viruses. Development of antibody to the Norwalk virus in the oyster outbreak, and the presence of large amounts of the smaller virus in a very high proportion of patients tested in the cockle outbreaks, does suggest that these different small round viruses are important. The Australian group were particularly fortunate in obtaining paired sera to investigate the antibody response to the two viruses they found; outbreaks of food-poisoning are normally regarded as bacterial in origin and acute serum is not routinely collected. The long incubation period, in excess of 30 hours, and the occurrence of secondary cases should alert investigators to the possibility of a viral cause. As a result of this large outbreak of NBGE new regulations have been introduced by the Government of New South Wales. Before marketing, oysters must be relayed for at least 48 hours in natural water free of pollution, or in tanks where the water has been exposed to ultraviolet light or ozone. This is already standard practice in the U.K. A useful guide to shellfish hygiene has been
published. 13 SMOOTH MUSCLE: SMALL IS BEAUTIFUL TOO STRIATED muscle has long twitched under the full glare of scientific interest. It fascinates because it has the elegant contractile structure which the two Huxleys discerned clearly and simultaneously a quarter of a century ago,1,2 and because it seems simply the compliant slave of our every conscious whim. Seems?-brief reflection shows that a great deal of striated muscle activity is not conscious at all, but automatic, like the movements of respiration and the adjustments of balance and posture
that accompany conscious movements. Smooth muscle looks dull and primitive in comparison. It has obvious interest for the ambitious young pharmacologist who notes that common and burdensome diseases such as asthma and hypertension go with disordered function of smooth muscle. The smooth muscle itself in the bronchus or the arteriole may be normal enough and the fault may lie in its control, just as sloth is not a disorder of striated muscle. But smooth muscle has in the past been so resistant to investigation that it has exasperated its most enthusiastic devotees; it was maddeningly inconsistent, and even reversed its response during experiments ;3 it was a "difficult tissue",4and it still has a very human tendency to spon13. Wood PC. Guide to shellfish hygiene. (WHO Offset Publication no. 31) Geneva: WHO. 1976. 1. Huxley AF, Niedergerke R. Structural changes in muscle during contraction. Nature
1977; 135: 20-27. 10. Appleton H, Buckley M, Thom BT, Cotton JL, Henderson S. Virus-like particles in winter vomiting disease. Lancet 1977; i: 409-11. 11. Christopher PJ, Grohmann GS, Millsom RH, Murphy AM. Parvovirus gastroenteritis—a new entity for Australia. Med J Aust 1978; i: 121-24. 12. Gerba CP, Goyal SM. Detection and occurrence of enteric viruses in shellfish; a review. J Food Protect 1978; 41: 743-54.
1954; 173: 971-73.
Hanson J. Changes in the cross striations of muscle during contraction and stretch and their interpretation. Nature 1954; 173: 973-76. 3. Bulbring E. Introduction. In: Bulbring E, Brading A, Jones A, Tomita T, eds. Smooth muscle. London: Arnold, 1970. 4. Needham M. Machina carnis. Cambridge: Cambridge University Press 1971: 545.
2.
Huxley HE,
1226
and
wholly predictable activity during pharmacological testing. taneous
not
Smooth muscle has been harder to understand than striated muscle for several reasons. Its cells are small and there is relatively more extracellular fluid. So the composition of the cell contents is harder to determine, and microelectrodes are less easy to insert and to maintain. Besides, smooth muscle is far more diverse than it looks. Admittedly, striated muscle is not all the same either. Some is faster and some slower; and occasionally odder varieties may occur, as in parts of the external ocular muscles.5 But smooth muscle is far more various. The major advances of recent years in understanding its complex mechanisms of control and contraction make fascinating contents for the current number of the British Medical Bulletin.6 Each striated muscle fibre receives excitation through a branch of a motor-nerve axon. A similar branch to control each smooth muscle cell would rarely be practicable ; there are far too many cells, and both excitation and inhibition may be required. Besides, the responsible nerve fibres do not need to be thick and thus rapidly conducting, since the business of smooth muscle is never as urgent as that of striated muscle. Thin nerve fibres would hardly support very numerous branches. A partial solution lies in the succession of varicosities along the nerve-fibre branches serving smooth muscle: transmitter is released from each varicosity, and thus one branch serves a whole territory along its length, not just the neighbourhood of its end. But some smooth muscle cannot be closely innervated at all. This happens in the inner part of arterial walls, where the arterial pressure would presumably squeeze the axoplasm back out of any nerve with the temerity to enter from the outside. The inner layers of the wall, though not closely innervated, are accessible to circulating’hormones in the lumen and to transmitter diffusing in from the outer layers. In addition, smooth muscle cells are electrically continuous with each other, generally through specialised gap junctions,’ and the contraction of one can evoke contraction in its neighbours. In the same way, the earthworm’s giant axon, which mediates avoidance of the early bird, is electrically continuous all the way down, despite "bulkheads" at every segment. Conduction from one smooth-muscle cell to another involves losses as a rule, so that it does not necessarily proceed very far. It can create a ring of contraction in an arteriole, but is not conveyed indefinitely up and down; the whole arteriole is not an all-or-none unit, and control instructions must travel along it by nerve and by circulating constituents in the blood in its lumen, not just by electrical conduction. In other smooth muscles-for instance, in the vas deferens, or in the uterus under oestrogen dominationpropagated action potentials are found and permit much more extensive spread of contraction from cell to cell. As well as responding to stimulation from nerve activity and from the activity of their neighbours, smooth mus-
respond to hormones, and they may also show spontaneous rhythmic contractions, as in the colonic taenia. There are striking species differences in the control of smooth muscle, and this is partly understandable
cle cells
organ may in a small animal in a large animal many, though the actual task of control is similar in the two and must be performed equally precisely. Thus in the m "*the cells of the vas deferens are each closely innervatea, 1.0.:’ not in the guineapig. The links between stimulation and the contractile mechanism inside the cell are better understood now. Knowledge of the protein components of the mechanism in smooth muscle is now approaching comparable knowledge in striated muscle. Higher calcium-ion concentration adjacent to the contractile proteins evokes contraction, but probably not through removing inhibition of ATPase activity by the troponin-tropomyosin systems; in smooth muscle the ATPase activity of purified actomyosin seems to be low and to need a boost during contraction. Where does the extra calcium for contraction come from? Some may come from outside the cell, and, in smooth muscles with action potentials, calcium ions seem to carry much of the inward current -an arrangement which employs calcium in two roles and economises in ion flow in cells which are small, have a large surface area, and are liable to osmotic imbalance unless fairly impermeable. Sodium-ion movements, so familiar in the mechanism of the nerve action potential, are not absent in smooth muscle, but may underlie the slow waves of electrical activity which occur in the stomach, the intestine, and the oestrogen-dominated uterus, and which differ from the spike action potentials also seen in these tissues. To reach their target and initiate contraction, calcium ions need to travel even less far if they can be released from within the cell instead of entering from outside. Smooth muscle has far less sarcoplasmic reticulum than striated muscle,9 but even in resting smooth muscle the intracellular calcium, if it were evenly distributed, would be enough to initiate maximal activity, and so is probably concentrated in the sarcoplasmic reticulum and other organelles, to be released when contraction occurs. Some can even be seen by electron microscopy apparently bound to the inner surface of the cell membrane, and then dispersed when contraction has been initiated.10 Thus some-but not all--of the calcium requirement for contraction is met from within and not from outside the cell. A remaining problem is to explain convincingly how calcium which enters the cell to initiate contraction is extruded again. Each type of smooth muscle now emerges as almost a law unto itself; it embodies its own variation on the possible sorts of control and contractile mechanism. This is frustrating for anyone who measures research achievement as grams of tissue explained per year of work. But it is encouraging for anyone looking for tools with which to work upon individual muscles to the exclusion of the since
one
and the
same
comprise few cells and
,
rest. 5. Harker D. Structure and innervation of sheep superior rectus and levator palpebrae extraocular muscles. I: extrafusal muscle fibres. Invest Ophthalmol Vis Sci 1973; 11: 956-67. 6. Bulbring E, Bolton TB, eds. Smooth muscle. British Medical Bulletin, 1979, Vol. 35, no 3. Published by the Medical Department, British Council, 65 Davies Street, London W1Y 2AA. £5, U.K.; $12.50, U.S.A. & Canada; £6 elsewhere. 7. Staehelin LA. Structure and function of intercellular junctions. Int Rev Cytol 1974; 39: 191-283.
8. Kao CY, Grundfest H. Postsynaptic electrogenesis in septate giant axons: I: earthworm median giant axon. J Neurophysiol 1957; 20: 553-73. 9. Devine CE, Somlyo AV, Somlyo AP. Sarcoplasmic reticulum and excitationcontraction coupling in mammalian smooth muscles.J Cell Biol 1972; 52: 690-718. 10. Sugi H, Daimon T. Translocation of intracellularly stored Ca during the contraction-relaxation cycle in guinea pig taenia coli. Nature 1977; 269: 436-38.
by conventional tissue-culture techbut several different viral agents have been niques, detected by electron microscopy in the fxces of affected people. This technique has proved useful in the investigation of gastroenteritis associated with seafood,2.3 and the latest instance was a very large outbreak in Australia associated with oysters. At least two thousand people were affected and the Norwalk virus was implicated.4 Norwalk was the first virus from human cases of NBGE to be seen electron microscopically.5 Unlike the rotavirus, which is mainly an infection of young children, Norwalk more often infects older children and adults and is believed by some to be a major cause of NBGE. Greenberg and co-workers, in the United States, judged that eight out of twenty-five outbreaks investigated were serologically associated with the Norwalk virus. Outbreaks associated with Norwalk virus are now being investigated in Britain. The mode of transmission is not clear; there have been reports indicating waterborne infectionbut the outbreak in Australia is the first in which infection has been shown to be foodborne. Norwalk is a small round virus of diameter around 27-32 nm; its density and other physicochemical properties suggest that it may belong to the parvovirus group,8 but this classification has not yet been confirmed by identification of the nucleic acid. In several specimens examined from the oyster-associated outbreak a second smaller virus particle, 22-25 nm in diameter, was observed. These particles are similar to those found in the cockle-associated gastroenteritis in England three years ago2 and similar particles have been observed in other outbreaks of NBGE, or "winter vomiting disease", where no food could be implicated.9-11 The particles retrieved in these outbreaks, although morphologically similar, seem to fall into four groups which are antigenically distinct from each other and also from the Norwalk virus. In both the Australian oyster-associated outbreak and the English cockle outbreak the apparent aetiological agents were not found in the shellfish themselves, although one batch of oysters contained the smaller 22-25 nm particle. Oysters and cockles, in common with all bivalve molluscs, can concentrate virus from polluted waters12 but the number of particles present in the shellcannot be grown
2.
Appleton H, Pereira MS. A possible virus aetiology in outbreaks of food poisoning from cockles. Lancet 1977; i: 780-81. 3. Murphy AM, Grohmann GS, Christopher PJ, Lopez WA, Millsom RH. Oyster food poisoning. Med J Aust 1978; ii: 439. 4. Murphy AM, Grohmann GS, Christopher PJ, Lopez WA, Davey GR, Millsom RH. An Australia-wide outbreak of gastroenteritis from oysters caused by Norwalk virus. Med J Aust 1979; ii: 329-33. 5. Kapikian AZ, Wyatt RG, Dolin R, Thornhill TS, Kalica AR, Chanock RM. Visualisation by immune electron microscopy of a 27 nm particle associated with acute infectious nonbacterial gastroenteritis. J Virol 1972; 10: 1075-81. 6. Greenberg HB, Valdesuso J, Yolken RH, et al. Role of Norwalk virus in outbreaks of nonbacterial gastroenteritis. J Infect Dis 1979; 139: 564-68. 7. Center for Disease Control. Morbid Mortal Weekly Rep 1978; 27: 403-04. 8. Kapikian AZ, Gerin JL, Wyatt RG, Thornhill TS, Chanock RM. Density in caesium chloride of the 27 nm "8F 11a" particle associated with acute infectious nonbacterial gastroenteritis: determination by ultracentrifugation and immune electron microscopy. Proc Soc Exp Biol Med 1973; 142: 874-77. 9. Thornhill TS, Wyatt RG, Kalica AR, Dolin R, Chanock RM, Kapikian AZ. Detection by immune electron microscopy of 26 to 27 nm virus-like particles associated with two family outbreaks of gastroenteritis. J Infect Dis
probably remains too low for detection by electron microscopy. In the Australian study an antibody response was detected only to the larger 27-30 nm particle, and the smaller 22-25 nm particle was believed to be unimportant (possibly even a bacteriophage). fish
However, it should be remembered that similar small
particles have been implicated in other outbreaks of NBGE in man and are known to have an important role in gastroenteritis of cattle, cats, and dogs. The presence of virus in faecal samples does not clinch the setiology since symptomless excretion is not unusual with gastroenteritis viruses. Development of antibody to the Norwalk virus in the oyster outbreak, and the presence of large amounts of the smaller virus in a very high proportion of patients tested in the cockle outbreaks, does suggest that these different small round viruses are important. The Australian group were particularly fortunate in obtaining paired sera to investigate the antibody response to the two viruses they found; outbreaks of food-poisoning are normally regarded as bacterial in origin and acute serum is not routinely collected. The long incubation period, in excess of 30 hours, and the occurrence of secondary cases should alert investigators to the possibility of a viral cause. As a result of this large outbreak of NBGE new regulations have been introduced by the Government of New South Wales. Before marketing, oysters must be relayed for at least 48 hours in natural water free of pollution, or in tanks where the water has been exposed to ultraviolet light or ozone. This is already standard practice in the U.K. A useful guide to shellfish hygiene has been
published. 13 SMOOTH MUSCLE: SMALL IS BEAUTIFUL TOO STRIATED muscle has long twitched under the full glare of scientific interest. It fascinates because it has the elegant contractile structure which the two Huxleys discerned clearly and simultaneously a quarter of a century ago,1,2 and because it seems simply the compliant slave of our every conscious whim. Seems?-brief reflection shows that a great deal of striated muscle activity is not conscious at all, but automatic, like the movements of respiration and the adjustments of balance and posture
that accompany conscious movements. Smooth muscle looks dull and primitive in comparison. It has obvious interest for the ambitious young pharmacologist who notes that common and burdensome diseases such as asthma and hypertension go with disordered function of smooth muscle. The smooth muscle itself in the bronchus or the arteriole may be normal enough and the fault may lie in its control, just as sloth is not a disorder of striated muscle. But smooth muscle has in the past been so resistant to investigation that it has exasperated its most enthusiastic devotees; it was maddeningly inconsistent, and even reversed its response during experiments ;3 it was a "difficult tissue",4and it still has a very human tendency to spon13. Wood PC. Guide to shellfish hygiene. (WHO Offset Publication no. 31) Geneva: WHO. 1976. 1. Huxley AF, Niedergerke R. Structural changes in muscle during contraction. Nature
1977; 135: 20-27. 10. Appleton H, Buckley M, Thom BT, Cotton JL, Henderson S. Virus-like particles in winter vomiting disease. Lancet 1977; i: 409-11. 11. Christopher PJ, Grohmann GS, Millsom RH, Murphy AM. Parvovirus gastroenteritis—a new entity for Australia. Med J Aust 1978; i: 121-24. 12. Gerba CP, Goyal SM. Detection and occurrence of enteric viruses in shellfish; a review. J Food Protect 1978; 41: 743-54.
1954; 173: 971-73.
Hanson J. Changes in the cross striations of muscle during contraction and stretch and their interpretation. Nature 1954; 173: 973-76. 3. Bulbring E. Introduction. In: Bulbring E, Brading A, Jones A, Tomita T, eds. Smooth muscle. London: Arnold, 1970. 4. Needham M. Machina carnis. Cambridge: Cambridge University Press 1971: 545.
2.
Huxley HE,
1226
and
wholly predictable activity during pharmacological testing. taneous
not
Smooth muscle has been harder to understand than striated muscle for several reasons. Its cells are small and there is relatively more extracellular fluid. So the composition of the cell contents is harder to determine, and microelectrodes are less easy to insert and to maintain. Besides, smooth muscle is far more diverse than it looks. Admittedly, striated muscle is not all the same either. Some is faster and some slower; and occasionally odder varieties may occur, as in parts of the external ocular muscles.5 But smooth muscle is far more various. The major advances of recent years in understanding its complex mechanisms of control and contraction make fascinating contents for the current number of the British Medical Bulletin.6 Each striated muscle fibre receives excitation through a branch of a motor-nerve axon. A similar branch to control each smooth muscle cell would rarely be practicable ; there are far too many cells, and both excitation and inhibition may be required. Besides, the responsible nerve fibres do not need to be thick and thus rapidly conducting, since the business of smooth muscle is never as urgent as that of striated muscle. Thin nerve fibres would hardly support very numerous branches. A partial solution lies in the succession of varicosities along the nerve-fibre branches serving smooth muscle: transmitter is released from each varicosity, and thus one branch serves a whole territory along its length, not just the neighbourhood of its end. But some smooth muscle cannot be closely innervated at all. This happens in the inner part of arterial walls, where the arterial pressure would presumably squeeze the axoplasm back out of any nerve with the temerity to enter from the outside. The inner layers of the wall, though not closely innervated, are accessible to circulating’hormones in the lumen and to transmitter diffusing in from the outer layers. In addition, smooth muscle cells are electrically continuous with each other, generally through specialised gap junctions,’ and the contraction of one can evoke contraction in its neighbours. In the same way, the earthworm’s giant axon, which mediates avoidance of the early bird, is electrically continuous all the way down, despite "bulkheads" at every segment. Conduction from one smooth-muscle cell to another involves losses as a rule, so that it does not necessarily proceed very far. It can create a ring of contraction in an arteriole, but is not conveyed indefinitely up and down; the whole arteriole is not an all-or-none unit, and control instructions must travel along it by nerve and by circulating constituents in the blood in its lumen, not just by electrical conduction. In other smooth muscles-for instance, in the vas deferens, or in the uterus under oestrogen dominationpropagated action potentials are found and permit much more extensive spread of contraction from cell to cell. As well as responding to stimulation from nerve activity and from the activity of their neighbours, smooth mus-
respond to hormones, and they may also show spontaneous rhythmic contractions, as in the colonic taenia. There are striking species differences in the control of smooth muscle, and this is partly understandable
cle cells
organ may in a small animal in a large animal many, though the actual task of control is similar in the two and must be performed equally precisely. Thus in the m "*the cells of the vas deferens are each closely innervatea, 1.0.:’ not in the guineapig. The links between stimulation and the contractile mechanism inside the cell are better understood now. Knowledge of the protein components of the mechanism in smooth muscle is now approaching comparable knowledge in striated muscle. Higher calcium-ion concentration adjacent to the contractile proteins evokes contraction, but probably not through removing inhibition of ATPase activity by the troponin-tropomyosin systems; in smooth muscle the ATPase activity of purified actomyosin seems to be low and to need a boost during contraction. Where does the extra calcium for contraction come from? Some may come from outside the cell, and, in smooth muscles with action potentials, calcium ions seem to carry much of the inward current -an arrangement which employs calcium in two roles and economises in ion flow in cells which are small, have a large surface area, and are liable to osmotic imbalance unless fairly impermeable. Sodium-ion movements, so familiar in the mechanism of the nerve action potential, are not absent in smooth muscle, but may underlie the slow waves of electrical activity which occur in the stomach, the intestine, and the oestrogen-dominated uterus, and which differ from the spike action potentials also seen in these tissues. To reach their target and initiate contraction, calcium ions need to travel even less far if they can be released from within the cell instead of entering from outside. Smooth muscle has far less sarcoplasmic reticulum than striated muscle,9 but even in resting smooth muscle the intracellular calcium, if it were evenly distributed, would be enough to initiate maximal activity, and so is probably concentrated in the sarcoplasmic reticulum and other organelles, to be released when contraction occurs. Some can even be seen by electron microscopy apparently bound to the inner surface of the cell membrane, and then dispersed when contraction has been initiated.10 Thus some-but not all--of the calcium requirement for contraction is met from within and not from outside the cell. A remaining problem is to explain convincingly how calcium which enters the cell to initiate contraction is extruded again. Each type of smooth muscle now emerges as almost a law unto itself; it embodies its own variation on the possible sorts of control and contractile mechanism. This is frustrating for anyone who measures research achievement as grams of tissue explained per year of work. But it is encouraging for anyone looking for tools with which to work upon individual muscles to the exclusion of the since
one
and the
same
comprise few cells and
,
rest. 5. Harker D. Structure and innervation of sheep superior rectus and levator palpebrae extraocular muscles. I: extrafusal muscle fibres. Invest Ophthalmol Vis Sci 1973; 11: 956-67. 6. Bulbring E, Bolton TB, eds. Smooth muscle. British Medical Bulletin, 1979, Vol. 35, no 3. Published by the Medical Department, British Council, 65 Davies Street, London W1Y 2AA. £5, U.K.; $12.50, U.S.A. & Canada; £6 elsewhere. 7. Staehelin LA. Structure and function of intercellular junctions. Int Rev Cytol 1974; 39: 191-283.
8. Kao CY, Grundfest H. Postsynaptic electrogenesis in septate giant axons: I: earthworm median giant axon. J Neurophysiol 1957; 20: 553-73. 9. Devine CE, Somlyo AV, Somlyo AP. Sarcoplasmic reticulum and excitationcontraction coupling in mammalian smooth muscles.J Cell Biol 1972; 52: 690-718. 10. Sugi H, Daimon T. Translocation of intracellularly stored Ca during the contraction-relaxation cycle in guinea pig taenia coli. Nature 1977; 269: 436-38.
