CaV1.2 sparklets in heart and vascular smooth muscle

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

CaV1.2 sparklets are local elevations in intracellular Ca2+ ([Ca2+]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 Ca2+ 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 Ca2+ influx, which strengthens excitation-contraction coupling in cardiac and vascular smooth muscle. This article is part of a Special Issue entitled "Calcium Signaling in Heart".

Original languageEnglish (US)
Pages (from-to)67-96
Number of pages30
JournalJournal of Molecular and Cellular Cardiology
Volume58
Issue number1
DOIs
StatePublished - May 2013

Fingerprint

Excitation Contraction Coupling
Vascular Smooth Muscle
Sarcolemma
Calcium Signaling
Calcineurin
Phosphoprotein Phosphatases
Cyclic AMP-Dependent Protein Kinases
Protein Kinases
Smooth Muscle
Membranes
Proteins
1,4-dihydropyridine
protein kinase C kinase

Keywords

  • Coupled gating
  • Hypertension
  • Total internal reflection fluorescence
  • Voltage-gated calcium channels

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

CaV1.2 sparklets in heart and vascular smooth muscle. / Navedo, Manuel F; Santana, Luis Fernando.

In: Journal of Molecular and Cellular Cardiology, Vol. 58, No. 1, 05.2013, p. 67-96.

Research output: Contribution to journalArticle

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