Isoprotrenol activates extracellular signal-regulated protein kinases in cardiomyocytes through calcineurin.

Signal-Regulated Protein Kinases in Cardiomyocytes Through Calcineurin To the Editor: Zou et al1 reported recently that isoproterenol activates extracellular signal-regulated protein kinases (ERK) in cardiomyocytes through calcineurin. The results mediated by -adrenergic receptors ( -AR) were convincing in neonatal cardiomyocytes but might not be applicable to adult cardiomyocytes, which undergo pathological hypertrophy. Communal et al2 demonstrated that ERK is not activated by isoproterenol using adult rat ventricular myocytes kept in culture for 16 hours. Recently, we made a similar observation using adult cardiomyocytes cultured for 48 hours.3 It is clear that signal transduction mediated by -AR and Gs and Gi coupling to -AR subtypes differs between adult and neonatal cardiomyocytes. The dosages of isoproterenol used to induce hypertrophy in neonatal cardiac myocytes in the study of Zou et al induces cardiomyocyte death by apoptosis rather than hypertrophy in adult cardiomyocytes.4,5 Although Zou et al reported similar activation of ERK by -AR stimulation in whole hearts, hypertrophy induced by in vivo administration of isoproterenol to transgenic mice is much more complicated than that seen in cultured myocytes because of systemic neurohormonal changes induced by -AR and contamination by non-myocyte cells. Therefore, further investigation is needed to verify that the cross-talk discussed in cultured neonatal cardiomyocytes induced by -AR is responsible for the hypertrophy seen in adult cardiomyocytes.