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Myotonia

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Persistent Inward Currents Play A Role In Muscle Dysfunction Seen In Myotonia Congenita, Ahmed Alaa Hawash Jan 2017

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 …


Persistent Inward Currents Play A Role In Muscle Dysfunction Seen In Myotonia Congenita, Ahmed Alaa Hawash Jan 2017

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 …