Egger, Caroline; Fernandez-Tenorio, Miguel; Blanch, Joaquim; Janicek, Radoslav; Egger, Marcel (2024). Dual mode of action of IP3-dependent SR-Ca2+ release on local and global SR-Ca2+ release in ventricular cardiomyocytes. Journal of molecular and cellular cardiology, 186, pp. 107-110. Elsevier 10.1016/j.yjmcc.2023.11.009
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In heart muscle, the physiological function of IP3-induced Ca2+ release (IP3ICR) from the sarcoplasmic reticulum (SR) is still the subject of intense study. A role of IP3ICR may reside in modulating Ca2+-dependent cardiac arrhythmogenicity. Here we observe the propensity of spontaneous intracellular Ca2+ waves (SCaW) driven by Ca2+-induced Ca2+ release (CICR) in ventricular myocytes as a correlate of arrhythmogenicity on the organ level. We observe a dual mode of action of IP3ICR on SCaW generation in an IP3R overexpression model. This model shows a mild cardiac phenotype and mimics pathophysiological conditions of increased IP3R activity. In this model, IP3ICR was able to increase or decrease the occurrence of SCaW depending on global Ca2+ activity. This IP3ICR-based regulatory mechanism can operate in two "modes" depending on the intracellular CICR activity and efficiency (e.g. SCaW and/or local Ryanodine Receptor (RyR) Ca2+ release events, respectively): a) in a mode that augments the CICR mechanism at the cellular level, resulting in improved excitation-contraction coupling (ECC) and ultimately better contraction of the myocardium, and b) in a protective mode in which the CICR activity is curtailed to prevent the occurrence of Ca2+ waves at the cellular level and thus reduce the probability of arrhythmogenicity at the organ level.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of Intensive Care, Emergency Medicine and Anaesthesiology (DINA) > University Emergency Center 04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Physiology |
UniBE Contributor: |
Egger, Caroline, Fernandez Tenorio, Miguel, Blanch Salvador, Joaquim, Janicek, Radoslav, Egger, Marcel |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
0022-2828 |
Publisher: |
Elsevier |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
23 Nov 2023 13:38 |
Last Modified: |
14 Jan 2024 00:15 |
Publisher DOI: |
10.1016/j.yjmcc.2023.11.009 |
PubMed ID: |
37993093 |
Uncontrolled Keywords: |
CICR Ca(2+) Sparks Ca(2+) puffs ECC RyR Ventricular myocytes |
BORIS DOI: |
10.48350/189301 |
URI: |
https://boris.unibe.ch/id/eprint/189301 |
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