Horn, Tamara; Ullrich, Nina D.; Egger, Marcel (2013). "Eventless" InsP 3 -dependent SR-Ca 2+ Release Affecting Atrial Ca 2+ Sparks. Journal of physiology, 591(8), pp. 2103-2111. Wiley-Blackwell 10.1113/jphysiol.2012.247288
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Augmented inositol 1,4,5-trisphosphate receptor (InsP3R) function has been linked to a variety of cardiac pathologies, including cardiac arrhythmia. The contribution of inositol 1,4,5-trisphosphate-induced Ca2+ release (IP3ICR) in excitation-contraction coupling (ECC) under physiological conditions, as well as under cellular remodelling, remains controversial. Here we test the hypothesis that local IP3ICR directly affects ryanodine receptor (RyR) function
and subsequent Ca2+-induced Ca2+ release in atrial myocytes. IP3ICR was evoked by UV-flash photolysis of caged InsP3 under whole-cell configuration of the voltage-clamp technique in atrial myocytes isolated from C57/BL6 mice. Photolytic release of InsP3 was accompanied by a significant increase in the Ca2+ release event frequency (4.14±0.72 vs. 6.20±0.76 events (100 μm)−1 s−1). These individual photolytically triggered Ca2+ release events were identified as Ca2+ sparks, which originated from RyR openings. This was verified by Ca2+ spark analysis and pharmacological separation between RyR and InsP3R-dependent sarcoplasmic reticulum (SR)-Ca2+ release (2-aminoethoxydiphenyl borate, xestospongin C, tetracaine). Significant
SR-Ca2+ flux but eventless SR-Ca2+ release through InsP3R were characterized using SR-Ca2+ leak/SR-Ca2+ load measurements. These results strongly support the idea that IP3ICR can effectively modulate RyR openings and Ca2+ spark probability. We conclude that eventless and highly efficient InsP3-dependent SR-Ca2+ flux is the main mechanism of functional cross-talk
between InsP3Rs and RyRs, which may be an important factor in the modulation of ECC sensitivity.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Physiology |
UniBE Contributor: |
Horn Lang, Tamara, Ullrich, Nina, Egger, Marcel |
Subjects: |
600 Technology > 610 Medicine & health 500 Science > 570 Life sciences; biology |
ISSN: |
0022-3751 |
Publisher: |
Wiley-Blackwell |
Language: |
English |
Submitter: |
Stefan von Känel-Zimmermann |
Date Deposited: |
13 Jun 2014 14:05 |
Last Modified: |
05 Dec 2022 14:30 |
Publisher DOI: |
10.1113/jphysiol.2012.247288 |
BORIS DOI: |
10.7892/boris.45853 |
URI: |
https://boris.unibe.ch/id/eprint/45853 |
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