Inositol 1,4,5-trisphosphate receptors and pacemaker rhythms
Yue-Kun Ju1, Elizabeth A Woodcock, David G Allen
1School of Medical Sciences and Bosch Institute, University of Sydney, Australia. ju@physiol.usyd.edu.au
Journal of Molecular and Cellular Cardiology
|June 21, 2012
Summary
Inositol 1,4,5-trisphosphate receptors (IP3Rs) may regulate heart rate by controlling intracellular calcium (Ca2+) oscillations. Emerging evidence suggests IP3Rs play a functional role in both normal and diseased hearts.
Area of Science:
- Cardiology
- Molecular Biology
- Physiology
Background:
- Intracellular Ca2+ is crucial for heart rate control, involving sarcoplasmic reticulum (SR) Ca2+ release via ryanodine receptors and Na+/Ca2+ exchanger activity.
- Inositol 1,4,5-trisphosphate receptors (IP3Rs) are SR Ca2+ release channels found in many cell types, including cardiac myocytes, but their role in heart rate regulation remains unclear.
Purpose of the Study:
- To review the emerging evidence for a functional role of IP3Rs in cardiac rhythm control.
- To explore how IP3R-mediated Ca2+ release contributes to intracellular Ca2+ oscillations and pacemaker activity.
Main Methods:
- Literature review of studies investigating IP3Rs in cardiac myocytes and pacemaker tissues.
- Analysis of mechanisms linking IP3R activity to membrane depolarization and cardiac rhythm.
Main Results:
- IP3 and IP3Rs are implicated in rhythm control in non-cardiac pacemaker tissues and embryonic hearts.
- IP3R-mediated Ca2+ release can generate intracellular Ca2+ oscillations, initiating membrane depolarization.
- Emerging evidence suggests IP3Rs contribute to cardiac rhythm regulation in normal and diseased hearts, potentially activating currents like the store-operated Ca2+ current.
Conclusions:
- IP3Rs represent a significant, yet underappreciated, factor in the complex regulation of heart rate.
- Further research into IP3R function could reveal new therapeutic targets for cardiac rhythm disorders.
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