J Neurophysiol (November 1, 2002). 10.1152/jn.00978.2001
Submitted on 29 November 2001
Accepted on 18 July 2002

Angiotensin AT₁-Receptors Depolarize Neonatal Spinal Motoneurons and Other Ventral Horn Neurons Via Two Different Conductances

 ¹National Institute on Drug Abuse, Intramural Research Program, Baltimore, Maryland 21224; and  ²Neurosciences, Ottawa Health Research Institute, University of Ottawa, Ottawa, Ontario K1Y 4E9 Canada

Oz, Murat and Leo P. Renaud. Angiotensin AT₁-Receptors Depolarize Neonatal Spinal Motoneurons and Other Ventral Horn Neurons Via Two Different Conductances. J. Neurophysiol. 88: 2857-2863, 2002. Angiotensin receptors are highly expressed in neonatal spinal cord. To identify their influence on neuronal excitability, we used patch-clamp recordings in spinal cord slices to assess responses of neonatal rat (5-12 days) ventral horn neurons to bath-applied angiotensin II (ANG II; 1 µM). In 14/34 identified motoneurons tested under current clamp, ANG II induced a slowly rising and prolonged membrane depolarization, blockable with Losartan (n = 5) and (Sar¹, Val⁵, Ala⁸)-ANG II (Saralasin, n = 4) but not PD123319 (1 µM each; n = 4). Under voltage clamp (V_H 65 mV), 7/22 motoneurons displayed an ANG-II-induced tetrodotoxin-resistant inward current (128 ± 31 pA) with a similar time course, an associated reduction in membrane conductance and net current reversal at 98.8 ± 3.9 mV. Losartan-sensitive ANG II responses were also evoked in 27/78 tested ventral horn "interneurons." By contrast with motoneurons, their ANG-II-induced inward current was smaller (39.9 ± 5.2 pA) and analysis of their I-V plots revealed three patterns. In eight cells, membrane conductance decreased with net inward current reversing at 103.8 ± 4.1 mV. In seven cells, membrane conductance increased with net current reversing at 37.9 ± 3.6 mV. In 12 cells, I-V lines remained parallel with no reversal within the current range tested. Intracellular dialysis with GTP--S significantly prolonged the ANG II effect in seven responsive interneurons and GDP--S significantly reduced the ANG II response in four other cells. Peak inward currents were significantly reduced in all 13 responding neurons recorded in slices incubated in pertussis toxin (5 µg/ml) for 12-18 h or in 12 neurons perfused with N-ethylmaleimide. Of 29 interneurons sensitive to pertussis toxin or N-ethylmaleimide treatment, 9 cells displayed a decrease in membrane conductance that reversed at 101.3 ± 3.8 mV. In eight cells, membrane conductance increased and reversed at 38.7 ± 3.4 mV. In 12 cells, the I-V lines remained parallel with no reversal within the current range tested, suggesting that both conductances are modulated by pertussis toxin-sensitive G proteins. These observations reveal a direct, G-protein-mediated depolarizing action of ANG II on neonatal rat ventral horn neurons. They also imply involvement of two distinct conductances that are differentially distributed among different cell types.