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Alterations in excitation-contraction in cardiac muscle from aged rats
j Mol Cell Cardiol 18 (Supplement 1) (1986) ~6ALTERATIONS IN EXCITATION-CONTRACTION IN CARDIAC MUSCLE FROM AGED RATS. E. G. Lakatta. Gerontology Research Center, National Institute on Aging, NIH, Baltimore, Maryland, U.S.A. The myocardium of normotensive rodents of advanced age exhibits a constellation of changes in excitation-contraction coupling mechanisms are similar to that produced by an experimentally induced chronic increase in left ventricular afterload in younger animals. These apparent age-related changes include (I) a twofold increase in the transmembrane action potential duration; (2) a 30% increase in the duration of the 9 2+ . . . . myoplasm~c Ca transient that occurs w~th excltatlon; (3) a 25% prolongation of z+ twitch duration; (4) a 50% reduction in the net Ca ~u~ping rate by isolated sarcoplasmic reticulum in the absence of a decrease in Ca stimulation of sarcoplasmic reticulum ATPase activity; (5) prolonged restitution of the excitation-contraction coupling cycle, manifested by an inability to respond to test stimuli at short coupling intervals; and (6) a marked reduction (to 25% of that in t h e ~ month animal) in the preparatlon of V 1 myosln Isozyme. The force response to Ca ~n myof~br~llar preparations and peak twitch force at optimal coupling intervals in intact preparations are unaltered in senescence but the velocity of isotonic shortening declines. An hypothesis to explain the similarities between aging and chronic pressure loading is that both the "aging process" and altered myocyte length_or loading as in experiz+ mental hypertension both involve a common messenger, e,g. Ca , which t~en stimulates an increase in myocyte mass and modulates other aspects of cell function. 9
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4 7 DEVELOPMENT OF ELECTRICAL ACTIVITY IN EMBRYONIC WR&RTS.
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SPERELAKIS.
DEPARTMENT OF PHYSIOLOGY & BIOPHYSICS, UNIVERS~[TY OF CINCINNATI COLLEGE OF MEDICINE, CINCINNATI, OHIO, U.S.A. Striking changes occur in electrical properties of the myocardial cell membrane during embryonic development of chick hearts. Young tubular hearts ($-3 days old) have a low resting potential, even though [ K] i is relatively high, eaused by a low K + permeabi!/ty (PK). The low P K also accounts for high automaticity. P K and resting potential increase dui'ing development, and automatieity of ventricular cells is suppressed. The young heart has a low (Na,K)-ATPase activity, and a very high cyclic A M P level Young hearts have Na+-dependent action potentials (APs), with slow maximal rates of rise (+Vmax), which are .not affected by tetrodotoxin (TTX); hyperpolarizat~on does not greatly increase Vma x. Young fetal rat hearts also have slowly-rising TTX-insensitiVe APs. Thus, functional fast Na § channels are absent or few in young hearts, the inward current during the A P being carried predominantly through slow ehannels. The slow APs are l~loeked bY verapamil, but not by M n $+. The eleetrieal properties of.voung hearts are similar to those of vlaseular smooth muscle. There is a pl'ogressive increase in +Vma x and number of fast Na + ehanne~ during development. By day 5, +Vma x is about 50-80 V/see. After day 8, T T X completely/abolishes excitability, suggestive that the number of functional slow channels has decreased Suffieiently so as not to support regenerative excitation. The number of [3H] T T X b~nding sites increases about 6-fuld during embryonic development in parallel with the increase in +Vmax, thus confirming that fast Na + channels increase during development.
4 8 T H E EMBRYONIC AND FETAL DEVELOPMENT OF THE HEART WITH PARTICULAR REFERENCE TO THE MYOCARDIAL CIRCULATION. Sz. Vir~gh and C.E. Challice. Department of Pathology, Postgraduate Medical School, Budapest 1389, Hungary, and Department of Physics, The University of Calgary, Calgary, Alberta, T2N IN4, Canada. This study describes the development of myocardial blood supply from simple irrigation of the myocardial wall by lumenal blood, to the mature arterial and venous systems. The first blood vessels develop simultaneously with the epicardium. Capillaries form by endocardial invaginations into the loose wall of the sinus venosus to the subepicardial space, where they quickly form a capillary network, notably in the sino-atrial groove, from which they develop toward the outflow tract. At the same time, trabeculae generating inwards from the outer ventricular walls consolidate into myocardium, thereby constricting the endocardial lining to form invaginations from the lumen. These occasionally penetrate the myocardium to reach the subepicardial space, notably at the interventricular (I-V) groove. At the intersection of the A-V and I-V grooves the primitive subepicardial capillaries meet to establish the early capillary network, primarily fed from the subepicardial region. Cells from the subepicardial investment become detached from the outer epicardial layer to form subepicardial connective tissue, beginning in the region of the sulcuses. The blood vessels and associated connective tissue contribute to the electrical insulation around the impulse conduction pathways, particularly the A-V node, His bundle, and the main trunks of arborization of the Purkinje system.
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4 7 DEVELOPMENT OF ELECTRICAL ACTIVITY IN EMBRYONIC WR&RTS.
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N.
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SPERELAKIS.
DEPARTMENT OF PHYSIOLOGY & BIOPHYSICS, UNIVERS~[TY OF CINCINNATI COLLEGE OF MEDICINE, CINCINNATI, OHIO, U.S.A. Striking changes occur in electrical properties of the myocardial cell membrane during embryonic development of chick hearts. Young tubular hearts ($-3 days old) have a low resting potential, even though [ K] i is relatively high, eaused by a low K + permeabi!/ty (PK). The low P K also accounts for high automaticity. P K and resting potential increase dui'ing development, and automatieity of ventricular cells is suppressed. The young heart has a low (Na,K)-ATPase activity, and a very high cyclic A M P level Young hearts have Na+-dependent action potentials (APs), with slow maximal rates of rise (+Vmax), which are .not affected by tetrodotoxin (TTX); hyperpolarizat~on does not greatly increase Vma x. Young fetal rat hearts also have slowly-rising TTX-insensitiVe APs. Thus, functional fast Na § channels are absent or few in young hearts, the inward current during the A P being carried predominantly through slow ehannels. The slow APs are l~loeked bY verapamil, but not by M n $+. The eleetrieal properties of.voung hearts are similar to those of vlaseular smooth muscle. There is a pl'ogressive increase in +Vma x and number of fast Na + ehanne~ during development. By day 5, +Vma x is about 50-80 V/see. After day 8, T T X completely/abolishes excitability, suggestive that the number of functional slow channels has decreased Suffieiently so as not to support regenerative excitation. The number of [3H] T T X b~nding sites increases about 6-fuld during embryonic development in parallel with the increase in +Vmax, thus confirming that fast Na + channels increase during development.
4 8 T H E EMBRYONIC AND FETAL DEVELOPMENT OF THE HEART WITH PARTICULAR REFERENCE TO THE MYOCARDIAL CIRCULATION. Sz. Vir~gh and C.E. Challice. Department of Pathology, Postgraduate Medical School, Budapest 1389, Hungary, and Department of Physics, The University of Calgary, Calgary, Alberta, T2N IN4, Canada. This study describes the development of myocardial blood supply from simple irrigation of the myocardial wall by lumenal blood, to the mature arterial and venous systems. The first blood vessels develop simultaneously with the epicardium. Capillaries form by endocardial invaginations into the loose wall of the sinus venosus to the subepicardial space, where they quickly form a capillary network, notably in the sino-atrial groove, from which they develop toward the outflow tract. At the same time, trabeculae generating inwards from the outer ventricular walls consolidate into myocardium, thereby constricting the endocardial lining to form invaginations from the lumen. These occasionally penetrate the myocardium to reach the subepicardial space, notably at the interventricular (I-V) groove. At the intersection of the A-V and I-V grooves the primitive subepicardial capillaries meet to establish the early capillary network, primarily fed from the subepicardial region. Cells from the subepicardial investment become detached from the outer epicardial layer to form subepicardial connective tissue, beginning in the region of the sulcuses. The blood vessels and associated connective tissue contribute to the electrical insulation around the impulse conduction pathways, particularly the A-V node, His bundle, and the main trunks of arborization of the Purkinje system.