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Oxytocin Downregulates the CaV1.2 L-Type Ca2+ Channel via Gi/cAMP/PKA/CREB Signaling Pathway in Cardiomyocytes
- Source :
- Membranes, Volume 11, Issue 4, Membranes, Vol 11, Iss 234, p 234 (2021)
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
Abstract
- Oxytocin (OT) and its receptor (OTR) are expressed in the heart and are involved in the physiological cardiovascular functional system. Although it is known that OT/OTR signaling is cardioprotective by reducing the inflammatory response and improving cardiovascular function, the role of OT in the cardiac electrical excitation modulation has not been clarified. This study investigates the molecular mechanism of the action of OT on cardiomyocyte membrane excitation focusing on the L-type Ca2+ channel. Our methodology uses molecular biological methods and a patch-clamp technique on rat cardiomyocytes with OT, combined with several signal inhibitors and/or activators. Our results show that long-term treatment of OT significantly decreases the expression of Cav1.2 mRNA, and reduces the L-type Ca2+ channel current (ICa.L) in cardiomyocytes. OT downregulates the phosphorylated component of a transcription factor adenosine-3′,5′-cyclic monophosphate (cAMP) response element binding protein (CREB), whose action is blocked by OTR antagonist and pertussis toxin, a specific inhibitor of the inhibitory GTP-binding regulators of adenylate cyclase, Gi. On the other hand, the upregulation of Cav1.2 mRNA expression by isoproterenol is halted by OT. Furthermore, inhibition of phospholipase C (PLC) was without effect on the OT action to downregulate Cav1.2 mRNA—which suggests a signal pathway of Gi/protein kinase A (PKA)/CREB mediated by OT/OTR. These findings indicate novel signaling pathways of OT contributing to a downregulation of the Cav1.2-L-type Ca2+ channel in cardiomyocytes.
- Subjects :
- L-type Ca2+ channel
Response element
Filtration and Separation
030204 cardiovascular system & hematology
lcsh:Chemical technology
CREB
Pertussis toxin
Cav1.2
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
oxytocin
Chemical Engineering (miscellaneous)
lcsh:TP1-1185
lcsh:Chemical engineering
Protein kinase A
Phospholipase C
biology
Chemistry
Process Chemistry and Technology
lcsh:TP155-156
gene transcription
Cell biology
biology.protein
Signal transduction
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 20770375
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Membranes
- Accession number :
- edsair.doi.dedup.....90670618fd7fcb071ddf85b4143173bb
- Full Text :
- https://doi.org/10.3390/membranes11040234