title: In vivo microscopy reveals extensive embedding of capillaries within the sarcolemma of skeletal muscle fibers.
abstract: OBJECTIVE
  To provide insight into mitochondrial function in vivo, we evaluated the 3D spatial relationship between capillaries, mitochondria, and muscle fibers in live mice.
  
  
  METHODS
  3D volumes of in vivo murine TA muscles were imaged by MPM. Muscle fiber type, mitochondrial distribution, number of capillaries, and capillary-to-fiber contact were assessed. The role of Mb-facilitated diffusion was examined in Mb KO mice. Distribution of GLUT4 was also evaluated in the context of the capillary and mitochondrial network.
  
  
  RESULTS
  MPM revealed that 43.6 ± 3.3% of oxidative fiber capillaries had ≥50% of their circumference embedded in a groove in the sarcolemma, in vivo. Embedded capillaries were tightly associated with dense mitochondrial populations lateral to capillary grooves and nearly absent below the groove. Mitochondrial distribution, number of embedded capillaries, and capillary-to-fiber contact were proportional to fiber oxidative capacity and unaffected by Mb KO. GLUT4 did not preferentially localize to embedded capillaries.
  
  
  CONCLUSIONS
  Embedding capillaries in the sarcolemma may provide a regulatory mechanism to optimize delivery of oxygen to heterogeneous groups of muscle fibers. We hypothesize that mitochondria locate to PV regions due to myofibril voids created by embedded capillaries, not to enhance the delivery of oxygen to the mitochondria.
authors.affiliation: Laboratory of Cardiac Energetics, NHLBI, Bethesda, Maryland, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Glancy
authors.forename: Li-Yueh
authors.initials: LY
authors.lastname: Hsu
authors.forename: Lam
authors.initials: L
authors.lastname: Dao
authors.forename: Matthew
authors.initials: M
authors.lastname: Bakalar
authors.forename: Stephanie
authors.initials: S
authors.lastname: French
authors.forename: David J
authors.initials: DJ
authors.lastname: Chess
authors.forename: Joni L
authors.initials: JL
authors.lastname: Taylor
authors.forename: Martin
authors.initials: M
authors.lastname: Picard
authors.forename: Angel
authors.initials: A
authors.lastname: Aponte
authors.forename: Mathew P
authors.initials: MP
authors.lastname: Daniels
authors.forename: Shervin
authors.initials: S
authors.lastname: Esfahani
authors.forename: Samuel
authors.initials: S
authors.lastname: Cushman
authors.forename: Robert S
authors.initials: RS
authors.lastname: Balaban
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D002196:Capillaries / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018715:Microscopy, Video; D008931:Mitochondria, Muscle / Q000235:genetics / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D012508:Sarcolemma / Q000378:metabolism*
chemical_list: D051275:Glucose Transporter Type 4; C495693:Slc2a4 protein, mouse; D010100:Oxygen
keywords: 3D quantitative imaging; GLUT4; microcirculation; muscle mitochondria; myoglobin; two-photon microscopy; vasculature