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pubmed:abstractText |
In nonexcitable cells, depletion of endoplasmic reticulum Ca(2+) stores leads to activation of plasma membrane Ca(2+) channels, a process termed capacitative Ca(2+) entry. Here, we demonstrate that this pathway functions in cells that also contain voltage-gated Ca(2+) channels, neonatal rat ventricular myocytes. The depletion of sarcoplasmic reticulum Ca(2+) stores elicited a prolonged increase in cytoplasmic Ca(2+) dependent on extracellular Ca(2+). Inhibitors of store-operated channels but not L-type channels diminished this response. The importance of this pathway to cardiac hypertrophy, which often is dependent on Ca(2+)/calmodulin-dependent transcription factors, was also assessed in this model. Hypertrophy and atrial natriuretic factor expression induced by angiotensin II or phenylephrine was more effectively attenuated by inhibitors of capacitative entry than of L-type channels. Additionally, cardiomyocytes were transfected with a construct encoding a fluorescent nuclear factor of activated T-cells chimeric protein to follow nuclear localization in response to thapsigargin, angiotensin II, and phenylephrine. This translocation was completely prevented by inhibitors of capacitative Ca(2+) entry and only partially abrogated by inhibitors of L-type channels. In contrast, a hypertrophic response induced by overexpression of the transcription factor MEK1 was unaffected by inhibitors of capacitative entry. Together, these data suggest a role for CCE in cardiomyocyte physiology and, in particular, in Ca(2+)-mediated cardiac hypertrophy.
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