Mar 28, 2020

Cold-Inducible RNA-Binding Protein Prevents an Excessive Heart Rate Response to Stress by Targeting Phosphodiesterase

Circulation Research
Duanyang XieYi-Han Chen

Abstract

Rationale: The stress response of heart rate (HR), which is determined by the plasticity of the sinus node (SAN), is essential for cardiac function and survival in mammals. As an RNA binding protein, cold-inducible RNA-binding protein (CIRP) can act as a stress regulator. Previously, we've documented that CIRP regulates cardiac electrophysiology at post-transcriptional level, suggesting its role in SAN plasticity, especially upon stress conditions. Objective: Our aim was to clarify the role of CIRP in SAN plasticity and HR regulation under stress conditions. Methods and Results: Telemetric ECG monitoring demonstrated an excessive acceleration of HR under isoprenaline (ISO) stimulation in conscious CIRP knockout (CIRP-KO) rats. Patch clamp analysis and confocal microscopic Ca2+ imaging of isolated SAN cells (SANCs) demonstrated that ISO stimulation induced a faster spontaneous firing rate in CIRP-KO SANCs than that in wild type (WT) SANCs. A higher concentration of cyclic adenosine monophosphate (cAMP), the key mediator of pacemaker activity, was detected in CIRP-KO SAN tissues than in WT SAN tissues. RNA-sequencing and quantitative real-time polymerase chain reaction (qPCR) analyses of single cells revealed that the 4B and 4D s...Continue Reading

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Mentioned in this Paper

Patch-Clamp Techniques
Knock-out
Protein Expression
Rolipram
CIRBP protein, human
Phosphodiesterase 5 inhibitor
RNA Processing, Post-Transcriptional
MRNA Binding
Isoproterenol
Quantitative Real-Time Polymerase Chain Reaction

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