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X-WR-CALNAME;VALUE=TEXT:ĢĒŠÄŌ­““
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DTSTART:20211107T020000
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DTSTART:20220313T020000
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UID:calendar.433931.field_event_date.0@www.wright.edu
DTSTAMP:20260219T165219Z
CREATED:20211202T145029Z
DESCRIPTION:Join us for Daniel Miranda's dissertation defense titledĀ ā€œAlter
 ed skeletal muscle excitation-contraction coupling in the R6/2 transgenic 
 mouse model for Huntingtonā€™s diseaseā€Huntingtonā€™s disease (HD) has classic
 ally been categorized as a neurodegenerative disorder. However\, the expre
 ssion of the disease-causing mutated huntingtin gene in skeletal muscle ma
 ycontribute to the symptoms of HD\, namely those that involve involuntary 
 muscle contraction. In the R6/2 transgenic mouse model of HD\, we previous
 ly observed ion channel defects that could contribute to involuntary muscl
 e contraction. Here\, in R6/2 muscle we investigated the consequence of th
 ese ion channel defects on action potentials (APs)\, the first step in exc
 itation-contraction (EC) coupling. We found that the ion channel defects w
 ere associated with depolarizing the baseline membrane potential during AP
  trains. We also observed changes in the AP waveform in R6/2 muscle\, incl
 uding a prolonged falling phase\, which was associated with reduced K+ cha
 nnel expression (another ion channel defect). Next\, we investigated the c
 onsequence of prolonged APs on intracellular Ca2+ release flux\, the secon
 d step in EC coupling. We observed an increase in Ca2+ release flux durati
 on\, which compensated for a reduction in peak Ca2+ release flux\, resulti
 ng in normal free Ca2+ (the Ca2+ available for contraction) in R6/2 muscle
 . Finally\, we investigated the consequence of prolonged APs and normal fr
 ee Ca2+ on muscle force generation\, the final step in EC coupling. We fou
 nd that\, when accounting for muscle atrophy\, the force generated by one 
 AP (twitch) was normal in R6/2 mice. This could be explained by the reduce
 d parvalbumin and normal free Ca2+ we observed in R6/2 muscle. We conclude
  that downregulation of K+ channels to prolong APs is a compensatory mecha
 nism for muscle weakness that leads to increased Ca2+ release duration and
  force production in R6/2 muscle. This is the first study to examine the e
 ntire EC coupling sequence in HD muscle\, revealing the importance of the 
 AP waveform in contributing to muscle force generation.
DTSTART;TZID=America/New_York:20211210T130000
DTEND;TZID=America/New_York:20211210T140000
LAST-MODIFIED:20211202T150601Z
LOCATION:101 NEC Bldg.
SUMMARY:Biomedical Sciences Ph.D. Program Dissertation Defense ā€œAltered ske
 letal muscle excitation-contraction coupling in the R6/2 transgenic mouse 
 model for Huntingtonā€™s diseaseā€
URL;TYPE=URI:/events/biomedical-sciences-phd-program-
 dissertation-defense-%E2%80%9Caltered-skeletal-muscle-excitation
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