Dual effects of angiotensin II on calcium currents in neonatal rat nodose neurons.
Angiotensin II (AII) reversibly modulates calcium current in isolated neonatal rat nodose ganglion cells by two different pathways. A maximum inhibitory effect of 43 +/- 6% (n = 25) of the peak calcium current at -10 mV was observed at 10 nM AII. The IC50 of the inhibitory response was 100 pM. Losartan, a specific antagonist for the AT1 type of AII receptor, abolished the AII-induced inhibition, as did preincubation with pertussis toxin (PTX). When omega-conotoxin GVIA (CTX) was added to the bath solution, AII produced no inhibition of the remaining calcium current, indicating that the AII inhibition was mediated through CTX-sensitive calcium channels. Reversible facilitation of calcium current was seen more rarely. The AII-induced facilitation was unaffected by losartan and PTX, indicating that the effect is mediated by a non-AT1 receptor and does not depend upon a PTX-sensitive G-protein. The facilitation is present when the CTX-sensitive current has been blocked and involves activation of a reserve pool of dihydropyridine (DHP)-sensitive channels. In general, a particular neuron exhibited either inhibition or facilitation. However, in some neurons both inhibition and facilitation could be demonstrated in the presence of the appropriate blocking agents.
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030.
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D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001713:Biphenyl Compounds / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D019808:Losartan; D008297:Male; D009474:Neurons / Q000502:physiology*; D009620:Nodose Ganglion / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology; D037342:Pertussis Toxin; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D020866:omega-Conotoxin GVIA
D001713:Biphenyl Compounds; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007093:Imidazoles; D010455:Peptides; D013777:Tetrazoles; D010566:Virulence Factors, Bordetella; D000804:Angiotensin II; D020866:omega-Conotoxin GVIA; D037342:Pertussis Toxin; D019808:Losartan