ANG II AT1 receptors induce depolarization and inward current in rat median preoptic neurons in vitro.
To examine ANG II receptors in rat median preoptic (MnPO) neurons, we used patch-clamp whole cell recordings in a parasagittal brain slice preparation. Lucifer yellow-filled neurons displayed a simple morphology with two to three aspiny dendrites. Bath-applied ANG II (1-2,000 nM for 30 s) induced a response in 37 of 70 cells. In current-clamp recordings, cells displayed a prolonged (10- to 30-min) depolarizing plateau with action potential discharges and an associated reduction in postburst afterhyperpolarization and spike frequency adaptation. In voltage-clamp recordings (holding potential -65 mV), cells displayed tetrodotoxin-resistant inward currents of 7. 6 +/- 1.9 (n = 5), 9.9 +/- 1.9 (n = 9), and 9.2 +/- 2.2 pA (n = 6) at 10, 200, and 2,000 nM, respectively. Responses were blockable by pretreatment with losartan (2 microM; n = 6) but not by PD-123177 (20 microM; n = 3). Net ANG II-induced current revealed a 7.8 +/- 0. 9% reduction in membrane conductance, decreasing but not reversing at hyperpolarized levels. Neurons expressing a strong hyperpolarization-activated, time-independent inward rectification were more likely to respond to ANG II. There was no correlation between the response of a neuron to ANG II and its response to norepinephrine.
Neurosciences, Loeb Research Institute, Ottawa Civic Hospital, and University of Ottawa, Ottawa, Ontario, Canada K1Y 4E9.
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D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D005456:Fluorescent Dyes; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007546:Isoquinolines; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011301:Preoptic Area / Q000166:cytology / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D005456:Fluorescent Dyes; D007093:Imidazoles; D007546:Isoquinolines; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C066253:PD 123177; D013779:Tetrodotoxin; C017475:lucifer yellow; D019808:Losartan