Constitutively active L-type Ca2+ channels

Manuel F Navedo, Gregory C. Amberg, V. Scott Votaw, Luis Fernando Santana

Research output: Contribution to journalArticlepeer-review

150 Scopus citations


Ca2+ influx through L-type Ca2+ channels (LTCCs) influences numerous physiological processes ranging from contraction in muscle and memory in neurons to gene expression in many cell types. However, the spatiotemporal organization of functional LTCCs has been nearly impossible to investigate because of methodological limitations. Here, we examined LTCC function with high temporal and spatial resolution using evanescent field fluorescence microscopy. Surprisingly, we found that LTCCs operated in functionally organized clusters, not necessarily as individual proteins. Furthermore, LTCC function in these clusters does not appear to be controlled by simple stochastic gating but instead by a PKC-dependent switch mechanism. This work suggests that resting intracellular free calcium concentration in arterial myocytes is predominantly controlled by this process in combination with rare voltage-dependent openings of individual LTCCs. We propose that Ca2+ influx via persistent LTCCs may be an important mechanism regulating steady-state local and global Ca2+ signals.

Original languageEnglish (US)
Pages (from-to)11112-11117
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number31
StatePublished - Aug 2 2005
Externally publishedYes


  • Evenescent field microscopy
  • Smooth muscle
  • Sparklets

ASJC Scopus subject areas

  • Genetics
  • General


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