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Persistent Inward Currents Play A Role In Muscle Dysfunction Seen In Myotonia Congenita, Ahmed Alaa Hawash
Persistent Inward Currents Play A Role In Muscle Dysfunction Seen In Myotonia Congenita, Ahmed Alaa Hawash
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Myotonia congenita is a rare skeletal muscle channelopathy caused by a reduced chloride channel (ClC-1) current, which results in debilitating muscle hyperexcitability, prolonged contractions, and transient episodes of weakness. The excitatory events that trigger myotonic action potentials in the absence of stabilizing ClC-1 current are not fully understood. My in vitro intracellular recordings from a mouse homozygous knockout of ClC-1 revealed a slow after-depolarization (AfD) that triggers myotonic action potentials. The AfD is well-explained by a tetrododoxin-sensitive and voltage-dependent Na+ persistent inward current (NaPIC). Notably, this NaPIC undergoes slow inactivation over seconds, thus providing the first mechanistic explanation for the …
Novel Mechanisms Underlying Warm-Up And Percussion Myotonia In Myotonia Congenita, Kevin Richard Nnovak
Novel Mechanisms Underlying Warm-Up And Percussion Myotonia In Myotonia Congenita, Kevin Richard Nnovak
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Patients with myotonia congenita have muscle hyperexcitability due to loss-of-function mutations in the ClC-1 chloride channel in skeletal muscle, which causes spontaneous firing of muscle action potentials (myotonia), producing muscle stiffness. Triggers for myotonia can occur voluntarily at the neuromuscular junction or involuntarily by striking the muscle with a reflex hammer (percussion myotonia). In patients, muscle stiffness lessens with exercise, a change known as the warm-up phenomenon. Our goal was to identify the mechanism underlying warm-up and percussion myotonia and to use this information to guide development of novel therapies. To determine these underlying mechanisms, we used a drug to …
Persistent Inward Currents Play A Role In Muscle Dysfunction Seen In Myotonia Congenita, Ahmed Alaa Hawash
Persistent Inward Currents Play A Role In Muscle Dysfunction Seen In Myotonia Congenita, Ahmed Alaa Hawash
Browse all Theses and Dissertations
Myotonia congenita is a rare skeletal muscle channelopathy caused by a reduced chloride channel (ClC-1) current, which results in debilitating muscle hyperexcitability, prolonged contractions, and transient episodes of weakness. The excitatory events that trigger myotonic action potentials in the absence of stabilizing ClC-1 current are not fully understood. My in vitro intracellular recordings from a mouse homozygous knockout of ClC-1 revealed a slow after-depolarization (AfD) that triggers myotonic action potentials. The AfD is well-explained by a tetrododoxin-sensitive and voltage-dependent Na+ persistent inward current (NaPIC). Notably, this NaPIC undergoes slow inactivation over seconds, thus providing the first mechanistic explanation for the …