Regulation of heart rate and the pacemaker current by phosphoinositide 3-kinase signaling
| Autor: | Evgeny P. Anyukhovsky, Richard Z. Lin, Lisa M. Ballou, Zhongju Lu, Ya-Ping Jiang, Hong Zhan Wang, Michael R. Rosen, Ira S. Cohen, Junyuan Gao |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Physiology Action Potentials 030204 cardiovascular system & hematology Second Messenger Systems 03 medical and health sciences Pacemaker potential Mice Phosphatidylinositol 3-Kinases 0302 clinical medicine Dogs Phosphatidylinositol Phosphates Biological Clocks Heart Rate Commentaries Heart rate medicine Animals PI3K/AKT/mTOR pathway Cells Cultured Sinoatrial Node Phosphoinositide 3-kinase biology Sinoatrial node Chemistry Diastolic depolarization medicine.disease 3. Good health Cell biology Mice Inbred C57BL Autonomic nervous system 030104 developmental biology medicine.anatomical_structure Heart failure biology.protein Commentary Rabbits |
| Zdroj: | The Journal of General Physiology |
| ISSN: | 1540-7748 |
| Popis: | Heart rate in physiological conditions is set by the sinoatrial node (SN), the primary cardiac pacing tissue. Phosphoinositide 3-kinase (PI3K) signaling is a major regulatory pathway in all normal cells, and its dysregulation is prominent in diabetes, cancer, and heart failure. Here, we show that inhibition of PI3K slows the pacing rate of the SN in situ and in vitro and reduces the early slope of diastolic depolarization. Furthermore, inhibition of PI3K causes a negative shift in the voltage dependence of activation of the pacemaker current, IF, while addition of its second messenger, phosphatidylinositol 3,4,5-trisphosphate, induces a positive shift. These shifts in the activation of IF are independent of, and larger than, those induced by the autonomic nervous system. These results suggest that PI3K is an important regulator of heart rate, and perturbations in this signaling pathway may contribute to the development of arrhythmias. |
| Databáze: | OpenAIRE |
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