CaV1.2 sparklets in heart and vascular smooth muscle.

Imagen de Manuel F Navedo
PDF versionPDF version
TítuloCaV1.2 sparklets in heart and vascular smooth muscle.
Publication TypeJournal Article
Year of Publication2013
AutoresNavedo, MF, Santana, LF
JournalJ Mol Cell Cardiol
Volume58
Pagination67-76
Date Published2013 May
ISSN1095-8584
Palabras claveCalcium, Calcium Channels, L-Type, Calcium Signaling, Humans, Membrane Potentials, Muscle, Smooth, Vascular, Signal Transduction
Abstract

CaV1.2 sparklets are local elevations in intracellular Ca(2+) ([Ca(2+)]i) resulting from the opening of a single or small cluster of voltage-gated, dihydropyridine-sensitive CaV1.2 channels. Activation of CaV1.2 sparklets is an early event in the signaling cascade that couples membrane depolarization to contraction (i.e., excitation-contraction coupling) in cardiac and arterial smooth muscle. Here, we review recent work on the molecular and biophysical mechanisms that regulate CaV1.2 sparklet activity in these cells. CaV1.2 sparklet activity is tightly regulated by a cohort of protein kinases and phosphatases that are targeted to specific regions of the sarcolemma by the anchoring protein AKAP150. We discuss a model for the local control of Ca(2+) influx via CaV1.2 channels in which a signaling complex formed by AKAP79/150, protein kinase C, protein kinase A, and calcineurin regulates the activity of individual CaV1.2 channels and also facilitates the coordinated activation of small clusters of these channels. This results in amplification of Ca(2+) influx, which strengthens excitation-contraction coupling in cardiac and vascular smooth muscle.

DOI10.1016/j.yjmcc.2012.11.018
Alternate JournalJ. Mol. Cell. Cardiol.
PubMed ID23220157
PubMed Central IDPMC3678956
Grant List1R01HL098200 / HL / NHLBI NIH HHS / United States
2R01HL085686 / HL / NHLBI NIH HHS / United States
2R01HL085870 / HL / NHLBI NIH HHS / United States
R01 HL085686 / HL / NHLBI NIH HHS / United States
R01 HL085870 / HL / NHLBI NIH HHS / United States
R01 HL098200 / HL / NHLBI NIH HHS / United States
T32 HL007828 / HL / NHLBI NIH HHS / United States