Stretch-elicited Na+/H+ exchanger activation: The autocrine/paracrine loop and its mechanical counterpart
The stretch of the cardiac muscle is immediately followed by an increase in the contraction strength after which occurs a slow force increase (SFR) that takes several minutes to fully develop. The SFR was detected in a wide variety of experimental preparations including isolated myocytes, papillary...
Guardado en:
| Autores principales: | , , , , |
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| Formato: | Articulo Revision |
| Lenguaje: | Inglés |
| Publicado: |
2003
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| Materias: | |
| Acceso en línea: | http://sedici.unlp.edu.ar/handle/10915/84584 |
| Aporte de: |
| Sumario: | The stretch of the cardiac muscle is immediately followed by an increase in the contraction strength after which occurs a slow force increase (SFR) that takes several minutes to fully develop. The SFR was detected in a wide variety of experimental preparations including isolated myocytes, papillary muscles and/or trabeculae, left ventricle strips of failing human myocardium, in vitro isovolumic and in vivo volume-loaded hearts. It was established that the initial increase in force is due to an increase in myofilament Ca<SUP>2+</SUP> responsiveness, whereas the SFR results from an increase in the Ca<SUP>2+</SUP> transient. However, the mechanism(s) for this increase in the Ca<SUP>2+</SUP> transient has remained undefined until the proposal of Na<SUP>+</SUP>/H<SUP>+</SUP> exchanger (NHE) activation by stretch. Studies in multicellular cardiac muscle preparations from cat, rabbit, rat and failing human heart have shown evidence that the stretch induces a rise in intracellular Na<SUP>+</SUP> ([Na<SUP>+</SUP>]<SUB>i</SUB>) through NHE activation, which subsequently leads to an increase in Ca<SUP>2+</SUP> transient via reverse-mode Na<SUP>+</SUP>/Ca<SUP>2+</SUP> (NCX) exchange. These experimental data agree with a theoretical ionic model of cardiomyocytes that predicted an increased Na<SUP>+</SUP> influx and a concurrent increase in Ca<SUP>2+</SUP> entry through NCX as the cause of the SFR to muscle stretch. However, there are aspects that await definitive demonstration, and perhaps subjected to species-related differences like the possibility of an autocrine/paracrine loop involving angiotensin II and endothelin as the underlying mechanism for stretch-induced NHE activation leading to the rise in [Na<SUP>+</SUP>]<SUB>i</SUB> and reverse-mode NCX. |
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