July 10, 2012PLoS ONEOpen Access

Splicing of the rSlo Gene Affects the Molecular Composition and Drug Response of Ca2+-Activated K+ Channels in Skeletal Muscle

Q: What is the clinical evidence from this study?

Population: Normal skeletal muscle physiology (preclinical) (n=6). Intervention: BK channel openers (e.g., bendroflumethiazide, resveratrol) vs. Control (no drug/vehicle). Primary outcome: BK channel activation and splice variant expression.

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Key result

Phenotype-dependent BK channel biophysical and pharmacological properties in rat skeletal muscle correlated with the expression levels of specific splice variants.

Population

Adult male Wistar rats, n=6, slow-twitch soleus and fast-twitch flexor digitorum brevis skeletal muscles.

Comparison

Patch-clamp experiments combined with transcript… vs Comparison between slow-twitch and fast-twitch…

Design

Preclinical

Authors

MDMaria Maddalena DinardoUniversity of Bari Aldo Moro GCGiulia Maria CamerinoOspedale di Civita Castellana AMAntonietta MeleUniversity of Bari Aldo Moro

Discussion

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Implication

Correlates BK properties with Kcnma1 splice variants in rat muscle; hypothesis-generating for phenotype-specific targeting, pending human validation.

Structured PICO

Population

6 adult male Wistar rats used to isolate slow-twitch and fast-twitch skeletal muscle fibers for in vitro patch-clamp and molecular analysis.

Intervention

Patch-clamp experiments combined with transcript scanning of the Kcnma1 gene and exposure to BK channel openers (e.g., NS1619, acetazolamide, bendroflumethiazide, resveratrol).

Comparator

Comparison between slow-twitch (Sol) and fast-twitch (FDB) muscles.

Outcome

Molecular composition (splice variants of Kcnma1 gene) and biophysical/pharmacological properties (drug responses) of BK channels.surrogate

Phenotype-dependent BK channel biophysical and pharmacological properties correlate with the expression levels of Kcnma1 splice variants in slow- and fast-twitch skeletal muscles.

Limitations

In vitro animal study, findings may not directly translate to human clinical conditions.

Cite This Study

Dinardo et al. (2012) studied Normal skeletal muscle physiology (preclinical) (n=6). BK channel openers (e.g., bendroflumethiazide, resveratrol) vs. Control (no drug/vehicle) was evaluated on BK channel activation and splice variant expression. Phenotype-dependent BK channel biophysical and pharmacological properties in rat skeletal muscle correlated with the expression levels of specific splice variants.

synapsesocial.com/papers/6a92ea385061e05975bb6548 https://doi.org/10.1371/journal.pone.0040235

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Implication

Correlates BK properties with Kcnma1 splice variants in rat muscle; hypothesis-generating for phenotype-specific targeting, pending human validation.

Splicing of the rSlo Gene Affects the Molecular Composition and Drug Response of Ca2+-Activated K+ Channels in Skeletal Muscle

Discussion

Member takes

Implication

Structured PICO

Limitations

Cite This Study

Splicing of the rSlo Gene Affects the Molecular Composition and Drug Response of Ca2+-Activated K+ Channels in Skeletal Muscle

Discussion

Member takes

Implication

Structured PICO

Limitations

Cite This Study

Also Consider

Also Consider