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The Relationship Between Myofilament Packing

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The Relationship Between Myofilament Packing View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by PubMed Central THE RELATIONSHIP BETWEEN MYOFILAMENT PACKING DENSITY AND SARCOMERE LENGTH IN FROG STRIATED MUSCLE PHILIP W. BRANDT, ENRIQUE LOPEZ, JOHN P. REUBEN, and HARRY GRUNDFEST From the Department of Anatomy and the Laboratory of Neurophysiology, the Department of Neurology, the College of Physicians & Surgeons of Columbia University, New York and the Marine Biological Laboratory, Woods Hole, Massachusetts. Dr. Lopez's present address is Instituto N. De Cardiologla, Mexico City, Mexico ABSTRACT In cross-sections of single fibers from the frog semitendinosus muscle the number of thick myofilaments per unit area (packing density) is a direct function of the sarcomere length. Our data, derived from electron microscopic studies, fit well with other data derived from in vivo, low-angle X-ray diffraction studies of whole semitendinosus muscles. The data are consistent with the assumption that the sarcomere of a fibril maintains a constant volume during changes in sarcomere length. The myofilament lattice, therefore, expands as the sarcomere shortens. Since the distance between adjacent myofilaments is an inverse square root function of sarcomere length, the interaction of the thick and the thin myofilaments during sarcomere shortening may occur over distances which increase 70 A or more, The "expanding-sarcomere, sliding-filament" model of sarcomere shortening is discussed in terms of the current concepts of muscle architecture and contraction. INTRODUCTION With contraction, striated muscle changes its microscopic studies on the relation between shape but maintains its volume almost perfectly. myofilament "packing density" and sarcomere Consistent with this fact, the sarcomere of a myo- length in single fibers of the semitendinosus muscle fibril thickens as it shortens (1), and also appears of the frog. The data show close agreement with to maintain a constant volume. The striation the X-ray findings, and require an expanding- changes which accompany changes in sarcomere sarcomere, sliding-filament model for striated length have been fitted to a sliding-filament model muscle. (2, 3) which has formed the basis for a hypothesis on the mechanism of muscle contraction (4). The METHODS model, however, does not take into account either Single fibers from the frog semitendinosus muscle the earlier light microscope observation of the were isolated by dissection. They were maintained at concomitant thickening and shortening of the different lengths in frog Ringer solution or were ex- sarcomere or the X-ray diffraction data which posed to a sequence of experimental solutions. In demonstrate that the myofilament lattice main- some of the solutions the chloride ion was replaced tains a constant volume during changes in sarco- isosmotically by propionate, which only transiently mere length (5-8). This paper reports electron affects the fiber volume (9). Other fibers were swollen 255 by immersion in a hyposomotic solution in which the crease in volume indicates a loss of intracellular ma- NaC1 concentration was reduced to one-half, or in terial, "loss phenomenon", (9). One fiber was shrunk isosomotic K-enriched media in which the Na + was in a medium made hyperosmotic by doubling the replaced by K +. Some fibers were exposed to hypo- NaC1 concentration. The control and the experi- smotic propionate media, and after return to the mental fibers were fixed by replacing the experimental isosmotic media their volumes were as much as 50% solution with cold (ice bath) Palade's osmium-tetrox- smaller than their initial control volumes. The de- ide fixative (10). TABLE I TABLE I--Continued Packing Density, Sarcomere Length, and Relative Average Relative lattice Lattice Volume sarcomere Packing volume after Exp. No. length density No. fixation Average Relative lattice sareomere Packing volume alter t~ (No.#~) SD (FL/2V) Exp. No. length density No. fixation 2. Whole muscles, glutaraldehyde fixative 110-1c 1.60 625 62 75 IS. (Noa.L~) SD (FL/N) 110-2c 1.77 800 30 65 1. Single fibers, Palade's OsO 4 fixative 117-1a 1.90 767.5 34 73 A. Isomotic saline 117-2a 2.12 842.5 56 73.5 59-10 2.78 700 78 116 l10-3f 2.21 840 63 75 59-11 2.23 680 97 96 117-3 2.46 820 37 84 59--12 2.86 790 58 106 110-7g 2.85 1030 99 80.5 61-1 2.64 904 83 81.5 117--4 3.03 1272.5 87 72.5 78-4 1.0 320 56 91 91-2 1.89 555 48 102 Avg 74.8% 95-7 2.26 645 74 98 95-8 2.64 853 87 90.5 The packing density, sarcomere length, and rela- tive lattice volume are listed for groups of single Avg 97.6% fibers exposed to a variety of experimental solutions B. Loss phenomena, shrunken then fixed in Palade's osmium tetroxide fixative, 59-14 2.19 675 37 95 and also for isolated fibers teased from the surface 73-2 3.06 778 57 115 of whole muscles fixed in glutaraldehyde dissolved 74-1 2.78 827 46 98.5 in Ringer solution. In part 1, the data refers to 76-1 2.26 790 -64 98.5 single fibers under the following experimental 95-3 2.33 804 49 84.5 conditions: (A) exposed to isosmotic chloride or propionate salines, (B) showing a volume loss Avg 98.2% averaging 40% before fixation obtained by ex- C.-60 Sodium, swollen posure to hyposmotic propionate media then re- 91-4 1.7 618 29 80.5 turn to control propionate media, see Methods, (C) 95-6 2.31 690 29 98 swollen about 60% in hyposomotic media prior to 95-9 2.28 738 53 90.5 fixation, (D) swollen and then reversed to normal volume before fixation, (E) swollen by exposure to Avg 89.6% iosomotic KC1 prior to fixation, (F) shrunken in D. Swollen and reversed media made hyperosmotic by doubling the NaC1 59-13 2.66 683 43 87 concentration. The whole muscles utilized for ob- 59-15 2.19 714 45 89.5 taining the data in part 2 were held at various lengths 59-16 2.26 645 23 102 in control Ringer solution and were fixed by sub- 73-1 2.55 593 40 110 stituting Ringer solution containing glutaraldehyde 74-2 2.99 818 67 106 After this fixation, single fibers were teased from 76-2 2.24 634 39 103 the surface, postfixed in osmium tetroxide, and then treated like the single fibers in part 1. The Avg 99.5% relative lattice volume after fixation is the ratio of E. Isosmotic KCL, swollen the lattice volume of the fiber, calculated from the 91-3 2.33 510 70 133% data in the Table, to the in vivo lattice volume, F. 2 X NaC1, shrunken calculated from the X-ray data (6). These volumes 95-10 2.19 928 58 69% are calculated according to the relationship V = FL/N. 256 TH~ JOURNAL OF CELL BIOLOGr • VOLUME 33, 1967 The effects of another fixative on the packing printed along with the micrographs of the fiber sec- density also were examined. Glutaraldehyde solutions tions. In both cases measurements were made on the were used to fix whole semitendinosus muscles, and prints. Average lengths for the sarcomere were deter- single fibers were teased from the surface of the muscle mined with a light microscope on 0.5 # thick longi- after 30 min fixation. Two different conditions of tudinal sections stained with teluidine blue. 20-30 fixation were used in these experiments. The control sarcomeres were averaged into each measurement. Ringer solation bathing the muscle was replaced for These measurements agreed within -4- 10% with 30 rain by a Ringer solution to which 0.2~0 glutaral- those made on single sarcomeres photographed in the dchydc was added. Then the mascles were fixed in electron microscope. Palade's fixative immediately or after an intermediate The packing density (number per /~2, termed 30 min step in 2~o glutaraldehydc in Ringer solution. "spacing" in an earlier report) (12) of the thick myo- There was no visible contraction of the muscles with filaments was determined from the cross-sections either method of glutaraldehyde fixation, whereas the through the A bands by counting the thick myofila- single fibers placed directly into Palade's fixative ments appearing in a square aperture representing usually contracted slightly. 0.04/fl of the original section. When one-half, or less, After 1-2 hr of osmium tetroxide fixation the fibers of a filament was exposed it was counted as one-half were dehydrated in graded ethanols to pure ethanol, a filament. 10 such areas were counted, with five washed with propylene oxide, and embedded in an different micrographs as sources. The number of thick Epon mixture (11) containing 4% dibutyl phthalate. myofilaments in each area, usually between 20 and The blocks were cut in half and the adjacent parts of 40, was multiplied by 25 to obtain the value for 1.0 the fibers were cut, respectively, in cross-section and #2. This figure was averaged with the other measure- in longitudinal section; the direction of the stroke was ments to obtain the packing density, and standard normal, to the long axis of the fiber. The sections deviations were calculated. were stained in uranyl acetate solutions followed by RESULTS lead hydroxide solutions, and were photographed in an RCA EMU 3C or Phillips 200 electron micro- Table I summarizes the measurements of the scope. The instrument was calibrated each time it was average sarcomere length, packing density, and used and the micrographs of the replica grating were calculated relative myofilament lattice volumes Separation 500A ~-" lO00- d z o~ 500- C i J u700 ,Io #.o 3'.0 Sarcomere length l~mva~.
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