Activation of β3-adrenoceptor increases the number of readily releasable glutamatergic vesicle via activating Ca2+/calmodulin/MLCK/myosin II pathway in the prefrontal cortex of juvenile rats
Abstract It is well known that β3-adrenoceptor (β3-AR) in many brain structures including prefrontal cortex (PFC) is involved in stress-related behavioral changes. SR58611A, a brain-penetrant β3-AR subtypes agonist, is revealed to exhibit anxiolytic- and antidepressant-like effects. Whereas activati...
Guardado en:
| Autores principales: | , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/4ca63b6736ed4ae498e6d3de95c30684 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| Sumario: | Abstract It is well known that β3-adrenoceptor (β3-AR) in many brain structures including prefrontal cortex (PFC) is involved in stress-related behavioral changes. SR58611A, a brain-penetrant β3-AR subtypes agonist, is revealed to exhibit anxiolytic- and antidepressant-like effects. Whereas activation of β3-AR exerts beneficial effects on cognitive function, the underlying cellular and molecular mechanisms have not been fully determined. In this study, whole cell patch-clamp recordings were employed to investigate the glutamatergic transmission of layer V/VI pyramidal cells in slices of the rat PFC. Our result demonstrated that SR58611A increased AMPA receptor-mediated excitatory postsynaptic currents (AMPAR-EPSCs) through activating pre-synaptic β3-AR. SR58611A enhanced the miniature EPSCs (mEPSCs) and reduced paired-pulse ratio (PPR) of AMPAR-EPSCs suggesting that SR58611A augments pre-synaptic glutamate release. SR58611A increased the number of readily releasable vesicle (N) and release probability (Pr) with no effects on the rate of recovery from vesicle depletion. Influx of Ca2+ through L-type Ca2+ channel contributed to SR58611A-mediated enhancement of glutamatergic transmission. We also found that calmodulin, myosin light chain kinase (MLCK) and myosin II were involved in SR58611A-mediated augmentation of glutamate release. Our current data suggest that SR58611A enhances glutamate release by the Ca2+/calmodulin/MLCK/myosin II pathway. |
|---|