Molecular and biophysical mechanisms of Ca2+ sparklets in smooth muscle.
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.
Santana
Luis F
LF
Department of Physiology and Biophysics, University of Washington, Box 357290, Seattle, WA 98195, USA. santana@u.washington.edu
Navedo
Manuel F
MF
D000818:Animals; D055592:Biophysical Phenomena; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020013:Calcium Signaling; D006801:Humans; D008564:Membrane Potentials; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*
D020746:Calcium Channels, L-Type; D011493:Protein Kinase C