Functional modulation of sarcolemmal KATP channels by atrial natriuretic peptide-elicited intracellular signaling in adult rabbit ventricular cardiomyocytes
| Autor: | Dai-Min Zhang, Yu-Fung Lin |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Intracellular Fluid medicine.drug_class Physiology Heart Ventricles Cells Medical Physiology 030204 cardiovascular system & hematology Ryanodine receptor 2 03 medical and health sciences 0302 clinical medicine Sarcolemma Atrial natriuretic peptide KATP Channels Ca2+/calmodulin-dependent protein kinase Natriuretic peptide medicine ryanodine receptor Animals Myocytes Cardiac Protein kinase A Cells Cultured reactive oxygen species Myocytes Cultured CaMKII Ryanodine receptor Chemistry Cell Biology Cytoprotection Cell biology ERK 030104 developmental biology cardiovascular system ANP signaling Rabbits Biochemistry and Cell Biology Cardiac Intracellular hormones hormone substitutes and hormone antagonists Atrial Natriuretic Factor Research Article Signal Transduction |
| Zdroj: | American journal of physiology. Cell physiology, vol 319, iss 1 Am J Physiol Cell Physiol |
| Popis: | ATP-sensitive potassium (KATP) channels couple cell metabolic status to membrane excitability and are crucial for stress adaptation and cytoprotection in the heart. Atrial natriuretic peptide (ANP), a cardiac peptide important for cardiovascular homeostasis, also exhibits cytoprotective features including protection against myocardial ischemia-reperfusion injuries. However, how ANP modulates cardiac KATP channels is largely unknown. In the present study we sought to address this issue by investigating the role of ANP signaling in functional modulation of sarcolemmal KATP (sarcKATP) channels in ventricular myocytes freshly isolated from adult rabbit hearts. Single-channel recordings were performed in combination with pharmacological approaches in the cell-attached patch configuration. Bath application of ANP markedly potentiated sarcKATP channel activities induced by metabolic inhibition with sodium azide, whereas the KATP-stimulating effect of ANP was abrogated by selective inhibition of the natriuretic peptide receptor type A (NPR-A), cGMP-dependent protein kinase (PKG), reactive oxygen species (ROS), extracellular signal-regulated protein kinase (ERK)1/2, Ca2+/calmodulin-dependent protein kinase II (CaMKII), or the ryanodine receptor (RyR). Blockade of RyRs also nullified hydrogen peroxide (H2O2)-induced stimulation of sarcKATP channels in intact cells. Furthermore, single-channel kinetic analyses revealed that ANP enhanced the function of ventricular sarcKATP channels through destabilizing the long closures and facilitating the opening transitions, without affecting the single-channel conductance. In conclusion, here we report that ANP positively modulates the activity of ventricular sarcKATP channels via an intracellular signaling mechanism consisting of NPR-A, PKG, ROS, ERK1/2, CaMKII, and RyR2. This novel mechanism may regulate cardiac excitability and contribute to cytoprotection, in part, by opening myocardial KATP channels. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|