BDNF contributes to angiotensin II-mediated reductions in peak voltage-gated K+ current in cultured CATH.a cells

Area of Science:

• Neuroscience
• Cardiovascular Physiology
• Molecular Signaling

Background:

• Elevated central angiotensin II (Ang II) contributes to sympathoexcitation in cardiovascular diseases like heart failure and hypertension.
• Ang II increases neuronal excitability partly by decreasing the voltage-gated, rapidly inactivating K(+) current (IA).
• Brain-derived neurotrophic factor (BDNF) also reduces IA and shares signaling pathways with Ang II.

Purpose of the Study:

• To investigate the hypothesis that Ang II-mediated suppression of voltage-gated K(+) currents (IA) involves brain-derived neurotrophic factor (BDNF) signaling.
• To elucidate the role of BDNF in Ang II's effect on neuronal excitability.

Main Methods:

• Whole-cell patch-clamp analysis was used on differentiated CATH.a catecholaminergic cells.
• Cells were treated with BDNF and Ang II to assess changes in IA.
• BDNF signaling was inhibited using an anti-BDNF antibody.
• The p38 MAPK pathway was inhibited using SB-203580.

Main Results:

• Both BDNF and Ang II treatments reduced IA in CATH.a cells.
• Pretreatment with an anti-BDNF antibody attenuated the Ang II-induced reduction of IA.
• Inhibition of p38 MAPK attenuated BDNF-mediated reductions in IA, suggesting a shared signaling component.

Conclusions:

• BDNF signaling is implicated in the Ang II-induced reduction of IA in CATH.a cells.
• BDNF may be a necessary mediator for Ang II to decrease IA, potentially increasing neuronal sensitivity and excitability.
• These findings offer insights into the mechanisms underlying sympathoexcitation in cardiovascular disease states.