Molecular and biophysical mechanisms of Ca2+ sparklets in smooth muscle.

Imagen de Manuel F Navedo
TítuloMolecular and biophysical mechanisms of Ca2+ sparklets in smooth muscle.
Publication TypeJournal Article
Year of Publication2009
AutoresSantana, LF, Navedo, MF
JournalJ Mol Cell Cardiol
Volume47
Issue4
Pagination436-44
Date Published2009 Oct
ISSN1095-8584
Palabras claveAnimals, Biophysical Phenomena, Calcium Channels, L-Type, Calcium Signaling, Humans, Membrane Potentials, Muscle, Smooth, Vascular, Protein Kinase C
Abstract

In this article, we review the biophysical basis and functional implications of a novel Ca(2+) signal (called "Ca(2+) sparklets") produced by Ca(2+) influx via L-type Ca(2+) channels (LTCCs) in smooth muscle. Ca(2+) sparklet activity is bimodal. In low activity mode, Ca(2+) sparklets are produced by random, brief openings of solitary LTCCs. In contrast, small clusters of LTCCs can function in a high activity mode that creates sites of continual Ca(2+) influx called "persistent Ca(2+) sparklets". Low activity and persistent Ca(2+) sparklets contribute to Ca(2+) influx in arterial, colonic, and venous smooth muscle. Targeting of PKCalpha by the scaffolding protein AKAP150 to specific sarcolemmal domains is required for the activation of persistent Ca(2+) sparklets. Calcineurin, which is also associated with AKAP150, opposes the actions of PKCalpha on Ca(2+) sparklets. At hyperpolarized potentials, Ca(2+) sparklet activity is low and hence does not contribute to global [Ca(2+)](i). Membrane depolarization increases low and persistent Ca(2+) sparklet activity, thereby increasing local and global [Ca(2+)](i). Ca(2+) sparklet activity is increased in arterial myocytes during hypertension, thus increasing Ca(2+) influx and activating the transcription factor NFATc3. We discuss a model for subcellular variations in Ca(2+) sparklet activity and their role in the regulation of excitation-contraction coupling and excitation-transcription coupling in smooth muscle.

DOI10.1016/j.yjmcc.2009.07.008
Alternate JournalJ. Mol. Cell. Cardiol.
PubMed ID19616004
PubMed Central IDPMC2739251
Grant ListR01 HL085870 / HL / NHLBI NIH HHS / United States
R01 HL085870-03 / HL / NHLBI NIH HHS / United States