Apelin acts in the subfornical organ to influence neuronal excitability and cardiovascular function
Article first published online: 28 MAY 2013
© 2013 The Authors. The Journal of Physiology © 2013 The Physiological Society
The Journal of Physiology
Volume 591, Issue 13, pages 3421–3432, July 2013
How to Cite
Dai, L., Smith, P. M., Kuksis, M. and Ferguson, A. V. (2013), Apelin acts in the subfornical organ to influence neuronal excitability and cardiovascular function. The Journal of Physiology, 591: 3421–3432. doi: 10.1113/jphysiol.2013.254144
- Issue published online: 1 JUL 2013
- Article first published online: 28 MAY 2013
- Accepted manuscript online: 29 APR 2013 07:10PM EST
- (Resubmitted 28 February 2013; accepted after revision 16 April 2013; first published online 29 April 2013)
- • Apelin receptor mRNA is expressed in the subfornical organ.
- • Apelin influences the excitability of the majority of subfornical organ neurons, with similar proportion showing depolarizing and hyperpolarizing effects.
- • Hyperpolarizations appear to result from the activation of a sustained voltage-activated potassium conductance, while depolarizations may result from modulation of a non-selective cationic conductance.
- • In vivo microinjection of apelin into the subfornical organ results in decreases in blood pressure.
Abstract Apelin is an adipocyte-derived hormone involved in the regulation of water balance, food intake and the cardiovascular system partially through actions in the CNS. The subfornical organ (SFO) is a circumventricular organ with identified roles in body fluid homeostasis, cardiovascular control and energy balance. The SFO lacks a normal blood–brain barrier, and is thus able to detect circulating signalling molecules such as angiotensin II and leptin. In this study, we investigated actions of apelin-13, the predominant apelin isoform in brain and circulatory system, on the excitability of dissociated SFO neurons using electrophysiological approaches, and determined the cardiovascular consequences of direct administration into the SFO of anaesthetized rats. Whole cell current clamp recording revealed that bath-applied 100 nm apelin-13 directly influences the excitability of the majority of SFO neurons by eliciting either depolarizing (31.8%, mean 7.0 ± 0.8 mV) or hyperpolarizing (28.6%, mean −10.4 ± 1.8 mV) responses. Using voltage-clamp techniques, we also identified modulatory actions of apelin-13 on specific ion channels, demonstrating that apelin-13 activates a non-selective cationic conductance to depolarize SFO neurons while activation of the delayed rectifier potassium conductance underlies hyperpolarizing effects. In anaesthetized rats, microinjection of apelin into SFO decreased both blood pressure (BP) (mean area under the curve −1492.3 ± 357.1 mmHg.s, n= 5) and heart rate (HR) (−32.4 ± 10.39 beats, n= 5). Our data suggest that circulating apelin can directly affect BP and HR as a consequence of the ability of this peptide to modulate the excitability of SFO neurons.