Constitutively active L-type Ca2+ channels.

Imagen de Manuel F Navedo
TítuloConstitutively active L-type Ca2+ channels.
Publication TypeJournal Article
Year of Publication2005
AutoresNavedo, MF, Amberg, GC, V Votaw, S, Santana, LF
JournalProc Natl Acad Sci U S A
Date Published2005 Aug 2
Palabras claveAnimals, Calcium Channels, L-Type, Calcium Signaling, Cerebral Arteries, Kinetics, Microscopy, Fluorescence, Myocytes, Smooth Muscle, Phorbol 12,13-Dibutyrate, Protein Kinase C, Rats

Ca(2+) influx through L-type Ca(2+) 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 Ca(2+) influx via persistent LTCCs may be an important mechanism regulating steady-state local and global Ca(2+) signals.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID16040810
PubMed Central IDPMC1180225
Grant ListHL 07312 / HL / NHLBI NIH HHS / United States
HL 077115 / HL / NHLBI NIH HHS / United States
HL 07828 / HL / NHLBI NIH HHS / United States