ProjectDissecting the impact of cGMP/cGKI interactors on cardiac diseases

Basic data

Dissecting the impact of cGMP/cGKI interactors on cardiac diseases
01/08/2024 to 31/07/2027
Abstract / short description:
cGMP-elevating agents require mitochondrial Ca2+-activated K+ channels of the BK type (mBK) to establish cardioprotection and mBK limits ischemia and reperfusion (I/R)-induced reactive oxygen species (ROS) formation. Mechanisms underlying the interactions between cGMP/cGMP-dependent protein kinase type I (cGKI), mBK, and ROS signaling in different cardiomyocyte (CM) compartments in vivo are unknown. We hypothesize that targeting of cGKI to I/R-exposed mitochondria and kinase activation depend on cGMP levels and oxidant-sensitive thiols within cGKI. To experimentally address this, infarct limiting properties of different cGMP pools and their ability to prevent post-infarction remodeling processes will be characterized. Therefore, wildtype mice and CM-specific cGKI knockouts as well as a disulfide-dead cGKI (cGKIKI/KI) mouse line lacking discrete oxidant-sensitive thiols will be utilized in combination with live-cell cGMP, Ca2+, K+ and ROS imaging approaches. To understand regulatory processes involving cGMP/cGKI in healthy vs post-infarction hearts, endogenous and pharmacologically modulated dynamics of cGMP signals and cGKI- vs cGKIKI/KI-associated protein complexes will be assessed globally and at subcellular locations of CMs. In doing so, we aim to expand our current knowledge of the cellular processes that contribute to cGMP signaling heterogeneity. Finally, our studies will pave the way for innovative research on novel cGKI interactors as important modifiers and targets in ischemic heart disease.

Involved staff


Faculty of Science
University of Tübingen
Pharmaceutical Institute
Department of Pharmacy and Biochemistry, Faculty of Science

Contact persons

Center for Ophthalmology
Hospitals and clinical institutes, Faculty of Medicine

Local organizational units

Department of Pharmacy and Biochemistry
Faculty of Science
University of Tübingen


Bonn, Nordrhein-Westfalen, Germany

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