Artículos de revistas
NFAT activation by membrane potential follows a calcium pathway distinct from other activity-related transcription factors in skeletal muscle cells
Fecha
2008-03Registro en:
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, Volume: 294, Issue: 3, Pages: C715-C725, 2008
0363-6143
Autor
Valdés, Juan Antonio
Gaggero, Eduardo
Hidalgo Tapia, Jorge
Leal, Nancy
Jaimovich Pérez, Enrique
Carrasco Friz, María Angélica
Institución
Resumen
Depolarization of skeletal muscle cells triggers intracellular calcium signals mediated by
ryanodine and IP3 receptors. We have reported that K+-induced depolarization activates the
transcriptional regulators ERKs, CREB, c-fos, c-jun and egr-1 through IP3-dependent calcium release,
whereas NF B activation is elicited by both ryanodine and IP3 receptors-mediated calcium signals. We
have further showed that field stimulation with electrical pulses results in an NF B activation increase
being it dependent of the amount of pulses and independent of their frequency.
In this work, we report the results obtained for NFAT-mediated transcription and translocation
generated by both K+ and electrical stimulation protocols in primary skeletal muscle cells and in
C2C12 cells. The calcium source for NFAT activation is through release by ryanodine receptors and
extracellular calcium entry. We found this activation to be independent on the number of pulses within
a physiological range of stimulus frequency and enhanced by long-lasting low frequency stimulation.
Therefore, activation of NFAT signaling pathway differs from that of NF B and other transcription
factors. Calcineurin enzyme activity correlates well with the relative activation of NFAT translocation
and transcription using different stimulation protocols. Furthermore, both K+-induced depolarization
and electrical stimulation increases mRNA levels of type 1 IP3 receptor mediated by calcineurin
activity, which suggests that depolarization may regulate IP3 receptor transcription.
These results confirm the presence of at least two independent pathways for excitationtranscription
coupling in skeletal muscle cells, both dependent on calcium release and triggered by the
same voltage sensor but activating different intracellular release channels.