SECTION I CELLULAR PHYSIOLOGY Childbirth A 24-year-old womn entered the hospital on the advice of her obstetrician because she was having strong labor pains at shorter and shorter intervals.On admission,physical examination revealed a normal pregnant woman in active labor and with dilation of the cervix of I to 2 cm Shortly thereafter,her neahranes ruptured,and she gave birth to a healthy 8-pound boy.Her postpartun course was unevent ful. 1.What are the funetional roles of smooth muscle in the uterus? 2.What types of patterns of contractile activity characterize the uterus? 3.Is soooth muscle differeat in nen and women? 4.What is the striking difference between smooth musele in reproductive organs and that in most other tissues? 5.During pregnancy,action potentials do not propagate over long distances in the myoretriun,and different areas of the myoretriun behave independently.Shortly before delivery the electrical and mechanical activity of the entire mrometrium becones synchronous.What changes in the sarcolerm muast occur to explain this change? 6.In what way is the relative absence of gap junctions during pregnancy and their presence at delivery functionally essemtial? 7.What changes at term might he the signal for the formation of gap junctions in the myometriun? 8.What is the myoplasmic second messenger involved in excitation-contraction coupling in the mrometrium? 9.What is the source of the Catt nobilized in response to action potentials? 10.Bow does an increase in the myoplasmic Ca++concentration produce contraction in myonetrial snooth suscle?
SECTION I CELLULAR PHYSIOLOGY Childbirth A 24-year-old woman entered the hospital on the advice of her obstetrician because she was having strong labor pains at shorter and shorter intervals. On admission, physical examination revealed a normal pregnant woman in active labor and with dilation of the cervix of 1 to 2 cm. Shortly thereafter, her membranes ruptured, and she gave birth to a healthy 8-pound boy. Her postpartum course was uneventful. 1. What are the functional roles of smooth muscle in the uterus? 2. What types of patterns of contractile activity characterize the uterus? 3. Is smooth muscle different in men and women? 4. What is the striking difference between smooth muscle in reproductive organs and that in most other tissues? 5. During pregnancy, action potentials do not propagate over long distances in the myometrium, and different areas of the myometrium behave independently. Shortly before delivery the electrical and mechanical activity of the entire myometrium becomes synchronous. What changes in the sarcolemma must occur to explain this change? 6. In what way is the relative absence of gap junctions during pregnancy and their presence at delivery functionally essential? 7. What changes at term might be the signal for the formation of gap junctions in the myometrium? 8. What is the myoplasmic second messenger involved in excitation-contraction coupling in the myometrium? 9. What is the source of the Ca++ mobilized in response to action potentials? 10. How does an increase in the myoplasmic Ca++ concentration produce contraction in myometrial smooth muscle?
11.Why is force not sustained,and why does the ayonetrium relax between phasic contractions? 12.Why are uterine contractions much slower than the cardiac contractions? 13.Does the cervical smooth musele relax in response to propagated action potentials? 14.What factors are responsible for the increase in myometrial mass during pregnancy? 15.What are the stiruli for mrometrial smooth muscle growth during pregnancy and for its postpartun reversal ANSVER 1.Contraction,proliferation.synthesis,and secretion of extracellular protein matrix. 2.Normally myometrial smooth musele is quiescent (relaxed),whereas cervical smooth muscle is tonically active:the latter activity serves a sphineter role.This pattern also characterizes pregnancy.Parturition is marked by rhythmic contractions of the mometriun with relaxation of cervical smooth muscle.Puberty. coitus,menses,and menopause are also associated with changes in uterine snooth muscle function. 3.Men lack uterine snooth musele,but they do have specifie types of saooth muscle in the urogenital systen with an eabryologic origin sinilar to uterine srooth muscle.The urogenital systen exhibits marked sexual dimorphism,but sex differences are nininal or absent in the snooth muscle of most organ systens. 4.At the functional level,the monetriu exhibits the same spectrun of contractile activity and properties characteristic of spooth muscle in general. However,the smooth muscle of the uterus and other parts of the reproductive system is notable in its dependence on,and response to.a variety of circulating hornoees (notably androgens and estrogens)
11. Why is force not sustained, and why does the myometrium relax between phasic contractions? 12. Why are uterine contractions much slower than the cardiac contractions? 13. Does the cervical smooth muscle relax in response to propagated action potentials? 14. What factors are responsible for the increase in myometrial mass during pregnancy? 15. What are the stimuli for myometrial smooth muscle growth during pregnancy and for its postpartum reversal ANSWER 1. Contraction, proliferation, synthesis, and secretion of extracellular protein matrix. 2. Normally myometrial smooth muscle is quiescent (relaxed), whereas cervical smooth muscle is tonically active; the latter activity serves a sphincter role. This pattern also characterizes pregnancy. Parturition is marked by rhythmic contractions of the myometrium with relaxation of cervical smooth muscle. Puberty, coitus, menses, and menopause are also associated with changes in uterine smooth muscle function. 3. Men lack uterine smooth muscle, but they do have specific types of smooth muscle in the urogenital system with an embryologic origin similar to uterine smooth muscle. The urogenital system exhibits marked sexual dimorphism, but sex differences are minimal or absent in the smooth muscle of most organ systems. 4. At the functional level, the myometrium exhibits the same spectrum of contractile activity and properties characteristic of smooth muscle in general. However, the smooth muscle of the uterus and other parts of the reproductive system is notable in its dependence on, and response to, a variety of circulating hormones (notably androgens and estrogens)
5.Propagation of action potentials in smooth muascle.as in cardiac muscle. requires low-resistance junctions between the cells.In fact,gap junctions in smooth muscles are sparse during pregnancy.but they form in large numbers shortly before delivery and persist for a short time after parturition. 6.All of the myometrial snooth muscle cells must comtract synchromously to reduce the volune of the uterus.This is achieved in most physically activated snooth muscles by electrical commmunication and the propagation of action potentials that originate from a pacemaker area.Contractions during pregnancy could induce miscarriages.Parturition requires forceful,coordinated activation and contraction. 7.The formation of gap junctions involves hormonal signals.However,their precise nature remains uncertain and is highly variable anong different mamalian species.A high progesterone to estrogen ratio is involved in maintaining uterine quiescence daring pregnancy. 8.It is the same as in all ruscles:increases in the intracellular Ca++ concentration. 9.In myometrial and other types of smooth muscle that generate action potentials. Cat+diffusion insard through voltage-gated channels is the major cause of depolarization.Thus Catt entry from the extracellular space can contribute to activation.However.the major source of activator Ca++for phasic contractions is the sarcoplasaic reticulum. 10.The Ca++binds to calmodulin,and the resulting calmodulin-Ca++complex binds to myosin kinase to activate this enzyme.Myosin kinase then phosphorylates a specific site on the crossbridges with P04 derived from the hydrolysis of ATP. Phosphorylated crossbridges are able to attach to the thim filanents and cycle,and thereby generate the contraction. 11.After the burst of action potentials.the myoplasnic Cat+concentration is reduced to low values by Ca++pungs and Na+/Ca++exchangers.Ca++dissociates from calnodulin.and myosin kinase reverts to its inactive form.The cross bridges are
5. Propagation of action potentials in smooth muscle, as in cardiac muscle, requires low-resistance junctions between the cells. In fact, gap junctions in smooth muscles are sparse during pregnancy, but they form in large numbers shortly before delivery and persist for a short time after parturition. 6. All of the myometrial smooth muscle cells must contract synchronously to reduce the volume of the uterus. This is achieved in most physically activated smooth muscles by electrical communication and the propagation of action potentials that originate from a pacemaker area. Contractions during pregnancy could induce miscarriages. Parturition requires forceful, coordinated activation and contraction. 7. The formation of gap junctions involves hormonal signals. However, their precise nature remains uncertain and is highly variable among different mammalian species. A high progesterone to estrogen ratio is involved in maintaining uterine quiescence during pregnancy. 8. It is the same as in all muscles: increases in the intracellular Ca++ concentration. 9. In myometrial and other types of smooth muscle that generate action potentials, Ca++ diffusion inward through voltage-gated channels is the major cause of depolarization. Thus Ca++ entry from the extracellular space can contribute to activation. However, the major source of activator Ca++ for phasic contractions is the sarcoplasmic reticulum. 10. The Ca++ binds to calmodulin, and the resulting calmodulin-Ca++ complex binds to myosin kinase to activate this enzyme. Myosin kinase then phosphorylates a specific site on the crossbridges with PO4 derived from the hydrolysis of ATP. Phosphorylated crossbridges are able to attach to the thin filaments and cycle, and thereby generate the contraction. 11. After the burst of action potentials, the myoplasmic Ca++ concentration is reduced to low values by Ca++ pumps and Na+/Ca++ exchangers. Ca++ dissociates from calmodulin, and myosin kinase reverts to its inactive form. The cross bridges are
inactivated enzymatically through the removal of the P04 group by myosin phosphatase. 12.First,a heartbeat is basically a twitch associated with a single action potential,whereas strong contractions of physically active single-unit smooth muscles are basically short tetani associated with a burst of action potentials. Second,the isoforms of myosin expressed in smooth mascle have intrinsically lower rates of ATP hydrolysis and crossbridge cycling.Third,covalent regulation by phosphorylation allows further reductions in cycling rates in latch.although this is of more significance for tonic smooth muscle. 13.No.The cervical relaxation associated with monetrial contraction reflects the fact that this tonic smooth muscle is not electrically coupled to the myometrium. The normally elevated myoplasmic Ca++that maintains tone and closure of the cervix is lowered as a result of reflex mechanisns that trigger relaxation. 14.All the elenents of the mometriun,including smooth muscle,blood vessels, other cell types,and the extracellular matrix,increase.Increases in smooth muscle mass result from proliferation (hyperplasia)and growth in cell size (hypertrophy). Smooth muascle also contributes to the extracellular matrix through synthesis and secretion of proteins,such as collagen. 15.These are poorly understood,diverse,and quite variable anong mamals.The gonadal steroids clearly are inportant
inactivated enzymatically through the removal of the PO4 group by myosin phosphatase. 12. First, a heartbeat is basically a twitch associated with a single action potential, whereas strong contractions of physically active single-unit smooth muscles are basically short tetani associated with a burst of action potentials. Second, the isoforms of myosin expressed in smooth muscle have intrinsically lower rates of ATP hydrolysis and crossbridge cycling. Third, covalent regulation by phosphorylation allows further reductions in cycling rates in latch, although this is of more significance for tonic smooth muscle. 13. No. The cervical relaxation associated with myometrial contraction reflects the fact that this tonic smooth muscle is not electrically coupled to the myometrium. The normally elevated myoplasmic Ca++ that maintains tone and closure of the cervix is lowered as a result of reflex mechanisms that trigger relaxation. 14. All the elements of the myometrium, including smooth muscle, blood vessels, other cell types, and the extracellular matrix, increase. Increases in smooth muscle mass result from proliferation (hyperplasia) and growth in cell size (hypertrophy). Smooth muscle also contributes to the extracellular matrix through synthesis and secretion of proteins, such as collagen. 15. These are poorly understood, diverse, and quite variable among mammals. The gonadal steroids clearly are important