@article{HoppeSartoriusChaikliengetal.2020,
  author    = {Hoppe, Kerstin and Sartorius, Tina and Chaiklieng, Sunisa and Wietzorrek, Georg and Ruth, Peter and Jurkat-Rott, Karin and Wearing, Scott and Lehmann-Horn, Frank and Klingler, Werner},
  title     = {Paxilline Prevents the Onset of Myotonic Stiffness in Pharmacologically Induced Myotonia: A Preclinical Investigation},
  series = {Frontiers in Physiology},
  volume    = {11},
  journal   = {Frontiers in Physiology},
  doi       = {10.3389/fphys.2020.533946},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218152},
  year      = {2020},
  abstract  = {Reduced Cl\(^{-}\) conductance causes inhibited muscle relaxation after forceful voluntary contraction due to muscle membrane hyperexcitability. This represents the pathomechanism of myotonia congenita. Due to the prevailing data suggesting that an increased potassium level is a main contributor, we studied the effect of a modulator of a big conductance Ca\(^{2+}\)- and voltage-activated K\(^{+}\) channels (BK) modulator on contraction and relaxation of slow- and high-twitch muscle specimen before and after the pharmacological induction of myotonia. Human and murine muscle specimens (wild-type and BK\(^{-/-}\)) were exposed to anthracene-9-carboxylic acid (9-AC) to inhibit CLC-1 chloride channels and to induce myotonia in-vitro. Functional effects of BK-channel activation and blockade were investigated by exposing slow-twitch (soleus) and fast-twitch (extensor digitorum longus) murine muscle specimens or human musculus vastus lateralis to an activator (NS1608) and a blocker (Paxilline), respectively. Muscle-twitch force and relaxation times (T\(_{90/10}\)) were monitored. Compared to wild type, fast-twitch muscle specimen of BK\(^{-/-}\) mice resulted in a significantly decreased T\(_{90/10}\) in presence of 9-AC. Paxilline significantly shortened T\(_{90/10}\) of murine slow- and fast-twitch muscles as well as human vastus lateralis muscle. Moreover, twitch force was significantly reduced after application of Paxilline in myotonic muscle. NS1608 had opposite effects to Paxilline and aggravated the onset of myotonic activity by prolongation of T\(_{90/10}\). The currently used standard therapy for myotonia is, in some individuals, not very effective. This in vitro study demonstrated that a BK channel blocker lowers myotonic stiffness and thus highlights its potential therapeutic option in myotonia congenital (MC).},
  language  = {en}
}
@article{ZulloFleckensteinSchleipetal.2020,
  author    = {Zullo, Alberto and Fleckenstein, Johannes and Schleip, Robert and Hoppe, Kerstin and Wearing, Scott and Klingler, Werner},
  title     = {Structural and Functional Changes in the Coupling of Fascial Tissue, Skeletal Muscle, and Nerves During Aging},
  series = {Frontiers in Physiology},
  volume    = {11},
  journal   = {Frontiers in Physiology},
  number    = {592},
  issn      = {1664-042X},
  doi       = {10.3389/fphys.2020.00592},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-206890},
  year      = {2020},
  abstract  = {Aging is a one-way process associated with profound structural and functional changes in the organism. Indeed, the neuromuscular system undergoes a wide remodeling, which involves muscles, fascia, and the central and peripheral nervous systems. As a result, intrinsic features of tissues, as well as their functional and structural coupling, are affected and a decline in overall physical performance occurs. Evidence from the scientific literature demonstrates that senescence is associated with increased stiffness and reduced elasticity of fascia, as well as loss of skeletal muscle mass, strength, and regenerative potential. The interaction between muscular and fascial structures is also weakened. As for the nervous system, aging leads to motor cortex atrophy, reduced motor cortical excitability, and plasticity, thus leading to accumulation of denervated muscle fibers. As a result, the magnitude of force generated by the neuromuscular apparatus, its transmission along the myofascial chain, joint mobility, and movement coordination are impaired. In this review, we summarize the evidence about the deleterious effect of aging on skeletal muscle, fascial tissue, and the nervous system. In particular, we address the structural and functional changes occurring within and between these tissues and discuss the effect of inflammation in aging. From the clinical perspective, this article outlines promising approaches for analyzing the composition and the viscoelastic properties of skeletal muscle, such as ultrasonography and elastography, which could be applied for a better understanding of musculoskeletal modifications occurring with aging. Moreover, we describe the use of tissue manipulation techniques, such as massage, traction, mobilization as well as acupuncture, dry needling, and nerve block, to enhance fascial repair.},
  language  = {en}
}