What question did this study set out to answer?

To determine whether Ca2+ influx through L-type voltage-gated Ca2+ channels regulates smooth muscle cell differentiation marker expression through a RhoA/Rho kinase-dependent pathway.

July 16, 2004Circulation Research

L-type Voltage-Gated Ca ²⁺ Channels Modulate Expression of Smooth Muscle Differentiation Marker Genes via a Rho Kinase/Myocardin/SRF–Dependent Mechanism

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To determine whether Ca2+ influx through L-type voltage-gated Ca2+ channels regulates smooth muscle cell differentiation marker expression through a RhoA/Rho kinase-dependent pathway.
Assessed smooth muscle myosin heavy chain (SMMHC), SM alpha-actin, and c-fos promoter activity in vascular smooth muscle cells under depolarization-induced channel activation.
Applied pharmacological inhibitors for voltage-gated Ca2+ channels (nifedipine), Rho kinase (Y-27632), and CaMK (KN93), combined with myocardin siRNA knockdown.
Performed chromatin immunoprecipitation (ChIP) assays to quantify serum response factor (SRF) binding to promoter CArG elements in intact chromatin.
Depolarization stimulated SMMHC and SM alpha-actin expression in a nifedipine-sensitive manner; this increase was prevented by Y-27632 but unaffected by KN93.
Depolarization upregulated myocardin and enhanced SRF enrichment at CArG promoter regions of SMMHC and SM alpha-actin, both of which were blocked by Y-27632 or myocardin siRNA.

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Implication

In vitro study demonstrates calcium influx drives smooth muscle gene expression via Rho kinase and myocardin, uncovering an excitation-transcription coupling mechanism.

Cite This Study

Wamhoff et al. (2004) studied this question.

synapsesocial.com/papers/6a7d3f2ca22b92c373279426 https://doi.org/10.1161/01.res.0000138582.36921.9e

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Implication

In vitro study demonstrates calcium influx drives smooth muscle gene expression via Rho kinase and myocardin, uncovering an excitation-transcription coupling mechanism.

L-type Voltage-Gated Ca ²⁺ Channels Modulate Expression of Smooth Muscle Differentiation Marker Genes via a Rho Kinase/Myocardin/SRF–Dependent Mechanism

Key Points

Discussion

Implication

Cite This Study

L-type Voltage-Gated Ca ²⁺ Channels Modulate Expression of Smooth Muscle Differentiation Marker Genes via a Rho Kinase/Myocardin/SRF–Dependent Mechanism

Key Points

Discussion

Implication

Cite This Study

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