Molecular and biophysical mechanisms of Ca2+ sparklets in smooth muscle

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

In this article, we review the biophysical basis and functional implications of a novel Ca2+ signal (called "Ca2+ sparklets") produced by Ca2+ influx via L-type Ca2+ channels (LTCCs) in smooth muscle. Ca2+ sparklet activity is bimodal. In low activity mode, Ca2+ 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 Ca2+ influx called "persistent Ca2+ sparklets". Low activity and persistent Ca2+ sparklets contribute to Ca2+ influx in arterial, colonic, and venous smooth muscle. Targeting of PKCα by the scaffolding protein AKAP150 to specific sarcolemmal domains is required for the activation of persistent Ca2+ sparklets. Calcineurin, which is also associated with AKAP150, opposes the actions of PKCα on Ca2+ sparklets. At hyperpolarized potentials, Ca2+ sparklet activity is low and hence does not contribute to global [Ca2+]i. Membrane depolarization increases low and persistent Ca2+ sparklet activity, thereby increasing local and global [Ca2+]i. Ca2+ sparklet activity is increased in arterial myocytes during hypertension, thus increasing Ca2+ influx and activating the transcription factor NFATc3. We discuss a model for subcellular variations in Ca2+ sparklet activity and their role in the regulation of excitation-contraction coupling and excitation-transcription coupling in smooth muscle.

Original languageEnglish (US)
Pages (from-to)436-444
Number of pages9
JournalJournal of Molecular and Cellular Cardiology
Volume47
Issue number4
DOIs
StatePublished - Oct 2009
Externally publishedYes

Keywords

  • AKAP
  • Arterial smooth muscle
  • Ca sparklets
  • NFAT
  • PKC
  • Portal vein

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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