Back to Search
Start Over
Stretch-Dependent Regulation of Calcium Signaling in Heart - Who are the Key Players?
- Source :
- Biophysical Journal. (2):322a
- Publisher :
- Biophysical Society. Published by Elsevier Inc.
-
Abstract
- An acute physiologic stretch of a cardiomyocyte triggers an increase in the production of reactive oxygen species (ROS) by the membrane-localized enzyme complex NADPH oxidase 2 (Nox2, X-ROS signaling). The ROS act locally to sensitize nearby Ca2+ release channels in the sarcoplasmic reticulum, the ryanodine receptors type 2 (RyR2), resulting in a brief increase in the frequency of calcium sparks. During sustained, cyclical stretch the rate of ROS production remains elevated and is graded by both the degree and frequency of cyclic stretch. The elevated ROS production results in a sustained increase of calcium spark rate, thus coupling the mechanical load on the heart cell to its calcium signaling sensitivity. However, an increase in RyR2 sensitivity alone is insufficient to explain a persistent increase in Ca2+ sparks, implicating additional stretch-dependent players in the sustained elevation of calcium signaling sensitivity with increased mechanical stress. We initially investigated three potential players based on their previous links to mechanical stress and modulation by ROS signaling. Here we report on the contribution of nitric oxide (NO), Ca2+/Calmodulin-dependent kinase II (CaMKII), and mechano-sensitive channels (MSC) on stretch-dependent regulation of calcium signaling in ventricular myocytes. We find that both NO and CaMKII have little to no effect on the rapid acute increase in the Ca2+ spark rate with stretch (≤10s), but each contribute significantly to maintaining elevated calcium signaling sensitivity with prolonged cyclic stretch (≥1min). We also explore the role of ROS signaling in the stretch-dependent activation of these signaling pathways, and how this affects both diastolic calcium sparks as well as systolic calcium transients and contractility in electrically paced myocytes.
- Subjects :
- Enzyme complex
medicine.medical_specialty
Ryanodine receptor
T-type calcium channel
Biophysics
chemistry.chemical_element
Calcium
Ryanodine receptor 2
Cell biology
Calcium sparks
Endocrinology
chemistry
Ca2+/calmodulin-dependent protein kinase
Internal medicine
cardiovascular system
medicine
Calcium signaling
Subjects
Details
- Language :
- English
- ISSN :
- 00063495
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Biophysical Journal
- Accession number :
- edsair.doi.dedup.....8a62709d8db5ede4b9318e25d0aa5ecf
- Full Text :
- https://doi.org/10.1016/j.bpj.2013.11.1858