Constitutively active L-type Ca2+ channels.
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.
Navedo
Manuel F
MF
Department of Physiology and Biophysics, University of Washington, Box 357290, Seattle, WA 98195, USA.
Amberg
Gregory C
GC
Votaw
V Scott
VS
Santana
Luis F
LF
D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002536:Cerebral Arteries / Q000166:cytology / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008856:Microscopy, Fluorescence; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats
D020746:Calcium Channels, L-Type; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C