TY - JOUR
T1 - Angiotensin II excites paraventricular nucleus neurons that innervate the rostral ventrolateral medulla
T2 - An in vitro patch-clamp study in brain slices
AU - Cato, Matthew J.
AU - Toney, Glenn M.
PY - 2005/1
Y1 - 2005/1
N2 - Neurons of the hypothalamic paraventricular nucleus (PVN) are key controllers of sympathetic nerve activity and receive input from angiotensin II (ANG II)-containing neurons in the forebrain. This study determined the effect of ANG II on PVN neurons that innervate in the rostral ventrolateral medulla (RVLM) - a brain stem site critical for maintaining sympathetic outflow and arterial pressure. Using an in vitro brain slice preparation, whole cell patch-clamp recordings were made from PVN neurons retrogradely labeled from the ipsilateral RVLM of rats. Of 71 neurons tested, 62 (87%) responded to ANG II. In current-clamp mode, bath-applied ANG II (2 μM) significantly (P < 0.05) depolarized membrane potential from -58.5 ± 2.5 to -54.5 ± 2.0 mV and increased the frequency of action potential discharge from 0.7 ± 0.3 to 2.8 ± 0.8 Hz (n = 4). Local application of ANG II by low-pressure ejection from a glass pipette (2 pmol, 0.4 nl, 5 s) also elicited rapid and reproducible excitation in 17 of 20 cells. In this group, membrane potential depolarization averaged 21.5 ± 4.1 mV, and spike activity increased from 0.7 ± 0.4 to 21.3 ± 3.3 Hz. In voltage-clamp mode, 41 of 47 neurons responded to pressure-ejected ANG II with a dose-dependent inward current that averaged -54.7 ± 3.9 pA at a maximally effective dose of 2.0 pmol. Blockade of ANG II AT1 receptors significantly reduced discharge (P < 0.001, n= 5), depolarization (P < 0.05, n = 3), and inward current (P < 0.01, n= 11) responses to locally applied ANG II. In six of six cells tested, membrane input conductance increased (P < 0.001) during local application of ANG II (2 pmol), suggesting influx of cations. The ANG II current reversed polarity at +2.2 ± 2.2 mV (n = 9) and was blocked (P < 0.01) by bath perfusion with gadolinium (Gd3+, 100 μM, n = 8), suggesting that ANG II activates membrane channels that are nonselectively permeable to cations. These findings indicate that ANGII excites PVN neurons that innervate the ipsilateral RVLM by a mechanism that depends on activation of AT1 receptors and gating of one or more classes of ion channels that result in a mixed cation current.
AB - Neurons of the hypothalamic paraventricular nucleus (PVN) are key controllers of sympathetic nerve activity and receive input from angiotensin II (ANG II)-containing neurons in the forebrain. This study determined the effect of ANG II on PVN neurons that innervate in the rostral ventrolateral medulla (RVLM) - a brain stem site critical for maintaining sympathetic outflow and arterial pressure. Using an in vitro brain slice preparation, whole cell patch-clamp recordings were made from PVN neurons retrogradely labeled from the ipsilateral RVLM of rats. Of 71 neurons tested, 62 (87%) responded to ANG II. In current-clamp mode, bath-applied ANG II (2 μM) significantly (P < 0.05) depolarized membrane potential from -58.5 ± 2.5 to -54.5 ± 2.0 mV and increased the frequency of action potential discharge from 0.7 ± 0.3 to 2.8 ± 0.8 Hz (n = 4). Local application of ANG II by low-pressure ejection from a glass pipette (2 pmol, 0.4 nl, 5 s) also elicited rapid and reproducible excitation in 17 of 20 cells. In this group, membrane potential depolarization averaged 21.5 ± 4.1 mV, and spike activity increased from 0.7 ± 0.4 to 21.3 ± 3.3 Hz. In voltage-clamp mode, 41 of 47 neurons responded to pressure-ejected ANG II with a dose-dependent inward current that averaged -54.7 ± 3.9 pA at a maximally effective dose of 2.0 pmol. Blockade of ANG II AT1 receptors significantly reduced discharge (P < 0.001, n= 5), depolarization (P < 0.05, n = 3), and inward current (P < 0.01, n= 11) responses to locally applied ANG II. In six of six cells tested, membrane input conductance increased (P < 0.001) during local application of ANG II (2 pmol), suggesting influx of cations. The ANG II current reversed polarity at +2.2 ± 2.2 mV (n = 9) and was blocked (P < 0.01) by bath perfusion with gadolinium (Gd3+, 100 μM, n = 8), suggesting that ANG II activates membrane channels that are nonselectively permeable to cations. These findings indicate that ANGII excites PVN neurons that innervate the ipsilateral RVLM by a mechanism that depends on activation of AT1 receptors and gating of one or more classes of ion channels that result in a mixed cation current.
UR - http://www.scopus.com/inward/record.url?scp=16644400212&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=16644400212&partnerID=8YFLogxK
U2 - 10.1152/jn.01055.2003
DO - 10.1152/jn.01055.2003
M3 - Article
C2 - 15356186
AN - SCOPUS:16644400212
SN - 0022-3077
VL - 93
SP - 403
EP - 413
JO - Journal of neurophysiology
JF - Journal of neurophysiology
IS - 1
ER -