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February 4, 2016Molecular Medicine ReportsOpen Access

The MAPK pathway is involved in the regulation of rapid pacing-induced ionic channel remodeling in rat atrial myocytes

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Population

Rat atrial myocytes isolated from 20 female Wistar rats (2-week-old)

Comparison

In vitro rapid pacing for up to 24 hours, with… vs Untreated cells or rapid pacing without inhibitors

Design

Preclinical

Follow-up

24 hours

Key result

Inhibition of the MAPK pathway with PD98059 and SB203580, or calcium channel blockade with verapamil, significantly attenuated rapid pacing-induced downregulation of LTCC-α1c and Kv4.3 expression.

Authors

WCWei ChengYZYun ZhuHWHaidong Wang

Discussion

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Member takes

Overview

Points to MAPK inhibition as a target against ionic remodeling in AF models; leaves open translation to human therapy.

Structured PICO

P
Population
In vitro study using atrial myocytes isolated from 20 female 2-week-old Wistar rats subjected to rapid pacing to model atrial fibrillation.
I
Intervention
In vitro rapid pacing (10 Hz, 1.5 V/cm) for up to 24 hours, with or without pretreatment with verapamil, PD98059 (ERK inhibitor), SB203580 (p38MAPK inhibitor), or their combination
C
Comparator
Untreated cells (routine culture without rapid pacing) or rapid pacing without inhibitors
O
Outcome
Intracellular Ca2+ concentration, mRNA and protein expression of LTCC-α1c and Kv4.3 potassium channels, and activation of ERK and p38MAPKsurrogate

Main Result

p-value: p=<0.01

The MAPK pathway mediates rapid pacing-induced ionic channel remodeling in rat atrial myocytes, highlighting a potential mechanism and therapeutic target for atrial fibrillation.

Limitations

  • Inhibitors could not totally rescue the expression of α1c and Kv4.3 to normal levels, suggesting other regulatory pathways exist.
  • In vitro model may not fully replicate in vivo atrial fibrillation.

Cite This Study

Cheng et al. (2016) studied Atrial fibrillation (rapid pacing model) (n=20). Verapamil, PD98059, and SB203580 vs. Untreated rapid pacing was evaluated on Intracellular Ca2+ concentration and ion channel protein expression (p=<0.01). Inhibition of the MAPK pathway with PD98059 and SB203580, or calcium channel blockade with verapamil, significantly attenuated rapid pacing-induced downregulation of LTCC-α1c and Kv4.3 expression.

synapsesocial.com/papers/6a89aa5ce0083a7c2c434273https://doi.org/10.3892/mmr.2016.4862
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