Cell volume control in phospholemman (PLM) knockout mice: do cardiac myocytes demonstrate a regulatory volume
James R Bell1, David Lloyd, Claire L Curl
1Cardiac Physiology, Cardiovascular Division, King's College London, The Rayne Institute, St Thomas' Hospital, London SE17EH, UK.
Experimental Physiology
|December 17, 2008
Summary
Phospholemman (PLM) does not appear essential for cardiac cell volume regulation in response to osmotic stress. However, PLM knockout hearts showed improved function when protected from osmotic challenges, suggesting a role in cardiac osmoregulation.
Area of Science:
- Cardiovascular Physiology
- Cellular Biology
- Membrane Transport
Background:
- Phospholemman (PLM) modulates Na+-K+-ATPase and is implicated in cell volume regulation, with 'PLM channels' showing taurine selectivity.
- Overexpression of PLM in non-cardiac cells increases taurine efflux and augments regulatory volume decrease (RVD).
- Cardiac PLM's role in osmoregulation is unstudied, despite observed depressed cardiac function in PLM knockout mice under osmotic stress.
Purpose of the Study:
- To investigate the role of phospholemman (PLM) in cardiac osmoregulation.
- To determine if PLM is essential for limiting water accumulation and mediating RVD in cardiomyocytes.
- To assess the impact of PLM deficiency on cardiac function during osmotic challenges.
Main Methods:
- Isolated hearts from wild-type and PLM knockout mice were perfused with crystalloid buffer, with and without mannitol, to assess contractile function.
- Isolated adult cardiomyocytes from both genotypes were subjected to hyposmotic challenges.
- Cell width was tracked using the IonOptix video edge-detection system to measure cell swelling.
- Regulatory volume decrease (RVD) capacity was assessed in freshly isolated and cultured adult and neonatal cardiomyocytes.
Main Results:
- Contractile function was improved in PLM knockout hearts perfused with mannitol, indicating a protective effect against osmotic stress.
- Cardiomyocytes from both genotypes swelled equally under hyposmotic conditions, suggesting PLM is not essential for limiting water entry.
- Freshly isolated adult cardiomyocytes failed to exhibit RVD, and short-term culture did not restore this response in either genotype.
Conclusions:
- Phospholemman (PLM) is not critical for preventing water accumulation in cardiomyocytes during hyposmotic stress.
- PLM may play a role in maintaining cardiac function under osmotic challenge, potentially independent of direct control over water entry.
- The inability of isolated adult cardiomyocytes to perform RVD highlights challenges in studying cardiac osmoregulation in vitro.
