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Decrease in maximal force generation in the neonatal mouse bladder corresponds to shift in myosin heavy chain isoform
Hsi-Yang Wu1, Stephen A Zderic, Alan J Wein
1Division of Pediatric Urology, Children's Hospital of Philadelphia, Pennsylvania, USA. wuhy@chp.edu
The Journal of Urology
|January 10, 2004
Summary
Neonatal bladders generate more force than adult bladders due to higher levels of myosin heavy chain isoform SM1. This myosin isoform decreases with age, correlating with reduced bladder force generation.
Area of Science:
- Physiology
- Developmental Biology
Background:
- Bladder force generation changes with development.
- Calcium handling alterations are a proposed cause for decreased force in neonatal bladders.
- Myosin heavy chain isoform SM1 is linked to increased force generation.
Purpose of the Study:
- To investigate the relationship between myosin heavy chain isoform SM1 levels and force generation in neonatal mouse bladders.
- To determine if decreased SM1 expression correlates with reduced bladder contractile function during development.
Main Methods:
- Studied contractile responses of bladder strips from mice (birth to 12 weeks) to KCl and bethanechol.
- Assessed rho-kinase activity inhibition using Y-27632.
- Quantified SM1/SM2 mRNA via RT-PCR and SM1 protein levels via SDS-PAGE.
- Determined muscle fraction using trichrome staining.
Main Results:
- Newborn bladders exhibited significantly higher tension than adult bladders in response to KCl and bethanechol.
- SM1 mRNA levels showed a slight decrease from 60% at birth to 50% at 12 weeks.
- SM1 protein levels decreased from 72.5% at birth to 50% by 3 weeks, remaining stable thereafter.
- Total myosin levels and muscle fraction remained relatively stable throughout development.
Conclusions:
- A decrease in SM1 expression was observed, correlating with reduced bladder force generation.
- Changes in myosin isoforms, specifically SM1, may play a role in the developmental decline of bladder voiding pressures.