Molecular and biophysical mechanisms of Ca2+ sparklets in smooth muscle.
Submitted by Manuel F Navedo on
Title | Molecular and biophysical mechanisms of Ca2+ sparklets in smooth muscle. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Santana, LF, Navedo, MF |
Journal | J Mol Cell Cardiol |
Volume | 47 |
Issue | 4 |
Pagination | 436-44 |
Date Published | 2009 Oct |
ISSN | 1095-8584 |
Keywords | Animals, 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. |
DOI | 10.1016/j.yjmcc.2009.07.008 |
Alternate Journal | J. Mol. Cell. Cardiol. |
PubMed ID | 19616004 |
PubMed Central ID | PMC2739251 |
Grant List | R01 HL085870 / HL / NHLBI NIH HHS / United States R01 HL085870-03 / HL / NHLBI NIH HHS / United States |