Angiotensin II regulates the activity of mouse suprachiasmatic nuclei neurons

T. M. Brown; E. McLachlan; H. D. Piggins

doi:10.1016/j.neuroscience.2008.03.068

Angiotensin II regulates the activity of mouse suprachiasmatic nuclei neurons

T. M. Brown, E. McLachlan, H. D. Piggins

Research output: Contribution to journal › Article › peer-review

Abstract

Neuropeptide signaling plays key roles in coordinating cellular activity within the suprachiasmatic nuclei (SCN), site of the master circadian oscillator in mammals. The neuropeptide angiotensin II (ANGII) and its cognate receptor AT1, are both expressed by SCN cells, but unlike other SCN neurochemicals, very little is known about the cellular actions of ANGII within this circadian clock. We used multi-electrode, multiunit, extracellular electrophysiology, coupled with whole-cell voltage and current clamp techniques to investigate the actions of ANGII in mouse SCN slices. ANGII (0.001-10 μM) dose dependently stimulated and inhibited extracellularly recorded neuronal discharge in many SCN neurons (∼60%). Both actions were blocked by pre-treatment with the AT1 receptor antagonist ZD7155 (0.03 μM), while suppressions but not activations were prevented by pre-treatment with the GABAA receptor antagonist bicuculline (20 μM). AT1 receptor blockade itself suppressed discharge in a subset (∼30%) of SCN neurons, and this action was not blocked by bicuculline. In voltage-clamped SCN neurons (-70 mV), AT1 receptor activation dose-dependently enhanced the frequency of action potential-driven, GABAA receptor-mediated currents, but did not alter their responses to exogenously applied GABA. In current-clamped SCN neurons perfused with tetrodotoxin, ANGII induced a membrane depolarization with a concomitant decrease in input resistance. In conclusion we show that AT1 receptor activation by ANGII depolarizes SCN neurons and stimulates action potential firing, leading to increased GABA release in the mouse SCN. Additionally we provide the first evidence that endogenous AT1 receptor signaling tonically regulates the activities of some SCN neurons. © 2008 IBRO.

Original language	English
Pages (from-to)	839-847
Number of pages	8
Journal	Neuroscience
Volume	154
Issue number	2
DOIs	https://doi.org/10.1016/j.neuroscience.2008.03.068
Publication status	Published - 23 Jun 2008

Keywords

circadian
extracellular
GABA
hypothalamus
neuropeptide
patch-clamp

Access to Document

10.1016/j.neuroscience.2008.03.068

Centre for Biological Timing
Lucas, R. (PI), Bechtold, D. (PI), Fustin, J.-M. (PI), Ashe, H. (PI), Brown, T. (PI), Blaikley, J. (PI), Brass, A. (PI), Chandola, T. (PI), Durrington, H. (PI), Else, K. (PI), Hepworth, M. (PI), Hunter, L. (PI), Kadler, K. (PI), Kitchen, G. (PI), Loudon, A. (PI), Macdonald, A. (PI), Mcbeth, J. (PI), Milosavljevic, N. (PI), Rattray, M. (PI), Rutter, M. (PI), Sharrocks, A. (PI), Spiller, D. (PI), Storchi, R. (PI), Belle, M. (PI), Meng, Q.-J. (PI), Allen, A. (PI), Dixon, W. (PI), Gibbs, J. (PI), Hazel, A. (PI), Papalopulu, N. (PI), Ray, D. (PI), White, M. (PI) & Chang, J. (PI)
Project: Research

Cite this

@article{f0cca61a5c284a528b2ab29c60af0a7e,

title = "Angiotensin II regulates the activity of mouse suprachiasmatic nuclei neurons",

abstract = "Neuropeptide signaling plays key roles in coordinating cellular activity within the suprachiasmatic nuclei (SCN), site of the master circadian oscillator in mammals. The neuropeptide angiotensin II (ANGII) and its cognate receptor AT1, are both expressed by SCN cells, but unlike other SCN neurochemicals, very little is known about the cellular actions of ANGII within this circadian clock. We used multi-electrode, multiunit, extracellular electrophysiology, coupled with whole-cell voltage and current clamp techniques to investigate the actions of ANGII in mouse SCN slices. ANGII (0.001-10 μM) dose dependently stimulated and inhibited extracellularly recorded neuronal discharge in many SCN neurons (∼60%). Both actions were blocked by pre-treatment with the AT1 receptor antagonist ZD7155 (0.03 μM), while suppressions but not activations were prevented by pre-treatment with the GABAA receptor antagonist bicuculline (20 μM). AT1 receptor blockade itself suppressed discharge in a subset (∼30%) of SCN neurons, and this action was not blocked by bicuculline. In voltage-clamped SCN neurons (-70 mV), AT1 receptor activation dose-dependently enhanced the frequency of action potential-driven, GABAA receptor-mediated currents, but did not alter their responses to exogenously applied GABA. In current-clamped SCN neurons perfused with tetrodotoxin, ANGII induced a membrane depolarization with a concomitant decrease in input resistance. In conclusion we show that AT1 receptor activation by ANGII depolarizes SCN neurons and stimulates action potential firing, leading to increased GABA release in the mouse SCN. Additionally we provide the first evidence that endogenous AT1 receptor signaling tonically regulates the activities of some SCN neurons. {\textcopyright} 2008 IBRO.",

keywords = "circadian, extracellular, GABA, hypothalamus, neuropeptide, patch-clamp",

author = "Brown, {T. M.} and E. McLachlan and Piggins, {H. D.}",

note = ", Biotechnology and Biological Sciences Research Council, United Kingdom",

year = "2008",

month = jun,

day = "23",

doi = "10.1016/j.neuroscience.2008.03.068",

language = "English",

volume = "154",

pages = "839--847",

journal = "Neuroscience",

issn = "0306-4522",

publisher = "Elsevier BV",

number = "2",

}

TY - JOUR

T1 - Angiotensin II regulates the activity of mouse suprachiasmatic nuclei neurons

AU - Brown, T. M.

AU - McLachlan, E.

AU - Piggins, H. D.

N1 - , Biotechnology and Biological Sciences Research Council, United Kingdom

PY - 2008/6/23

Y1 - 2008/6/23

N2 - Neuropeptide signaling plays key roles in coordinating cellular activity within the suprachiasmatic nuclei (SCN), site of the master circadian oscillator in mammals. The neuropeptide angiotensin II (ANGII) and its cognate receptor AT1, are both expressed by SCN cells, but unlike other SCN neurochemicals, very little is known about the cellular actions of ANGII within this circadian clock. We used multi-electrode, multiunit, extracellular electrophysiology, coupled with whole-cell voltage and current clamp techniques to investigate the actions of ANGII in mouse SCN slices. ANGII (0.001-10 μM) dose dependently stimulated and inhibited extracellularly recorded neuronal discharge in many SCN neurons (∼60%). Both actions were blocked by pre-treatment with the AT1 receptor antagonist ZD7155 (0.03 μM), while suppressions but not activations were prevented by pre-treatment with the GABAA receptor antagonist bicuculline (20 μM). AT1 receptor blockade itself suppressed discharge in a subset (∼30%) of SCN neurons, and this action was not blocked by bicuculline. In voltage-clamped SCN neurons (-70 mV), AT1 receptor activation dose-dependently enhanced the frequency of action potential-driven, GABAA receptor-mediated currents, but did not alter their responses to exogenously applied GABA. In current-clamped SCN neurons perfused with tetrodotoxin, ANGII induced a membrane depolarization with a concomitant decrease in input resistance. In conclusion we show that AT1 receptor activation by ANGII depolarizes SCN neurons and stimulates action potential firing, leading to increased GABA release in the mouse SCN. Additionally we provide the first evidence that endogenous AT1 receptor signaling tonically regulates the activities of some SCN neurons. © 2008 IBRO.

AB - Neuropeptide signaling plays key roles in coordinating cellular activity within the suprachiasmatic nuclei (SCN), site of the master circadian oscillator in mammals. The neuropeptide angiotensin II (ANGII) and its cognate receptor AT1, are both expressed by SCN cells, but unlike other SCN neurochemicals, very little is known about the cellular actions of ANGII within this circadian clock. We used multi-electrode, multiunit, extracellular electrophysiology, coupled with whole-cell voltage and current clamp techniques to investigate the actions of ANGII in mouse SCN slices. ANGII (0.001-10 μM) dose dependently stimulated and inhibited extracellularly recorded neuronal discharge in many SCN neurons (∼60%). Both actions were blocked by pre-treatment with the AT1 receptor antagonist ZD7155 (0.03 μM), while suppressions but not activations were prevented by pre-treatment with the GABAA receptor antagonist bicuculline (20 μM). AT1 receptor blockade itself suppressed discharge in a subset (∼30%) of SCN neurons, and this action was not blocked by bicuculline. In voltage-clamped SCN neurons (-70 mV), AT1 receptor activation dose-dependently enhanced the frequency of action potential-driven, GABAA receptor-mediated currents, but did not alter their responses to exogenously applied GABA. In current-clamped SCN neurons perfused with tetrodotoxin, ANGII induced a membrane depolarization with a concomitant decrease in input resistance. In conclusion we show that AT1 receptor activation by ANGII depolarizes SCN neurons and stimulates action potential firing, leading to increased GABA release in the mouse SCN. Additionally we provide the first evidence that endogenous AT1 receptor signaling tonically regulates the activities of some SCN neurons. © 2008 IBRO.

KW - circadian

KW - extracellular

KW - GABA

KW - hypothalamus

KW - neuropeptide

KW - patch-clamp

U2 - 10.1016/j.neuroscience.2008.03.068

DO - 10.1016/j.neuroscience.2008.03.068

M3 - Article

C2 - 18479832

SN - 0306-4522

VL - 154

SP - 839

EP - 847

JO - Neuroscience

JF - Neuroscience

IS - 2

ER -

Angiotensin II regulates the activity of mouse suprachiasmatic nuclei neurons

Abstract

Keywords

Access to Document

Fingerprint

Projects

Centre for Biological Timing

Cite this