title: Alpha-adrenergic modulation of ionic currents in cultured parasympathetic neurons from rat intracardiac ganglia.
abstract: 1. Modulation of ionic conductances by alpha-adrenergic agonists was investigated in cultured parasympathetic neurons from rat intracardiac ganglia. Application of norepinephrine (NE, 25-100 microM) to the soma of isolated neurons reversibly reduced both the amplitude and duration of the Ca(2+)-dependent action potential evoked by injection of depolarizing current when Na+ and K+ currents were blocked pharmacologically. 2. In the whole-cell voltage-clamp mode, application of NE reversibly reduced the amplitude and rate of activation of Ca2+ current (ICa). The amplitude inhibition was greater at the peak of the current (55%) than at the end of a 700-ms pulse (20%). Maximal doses of NE produced only approximately 60% inhibition of peak ICa amplitude. 3. Inactivation of ICa was best fit by the sum of two exponential functions in the absence of NE, but was described by a single exponential function in the presence of NE. These results suggest that NE preferentially inhibited a fast inactivating component of the Ca2+ current in these parasympathetic neurons. 4. NE reversibly reduced the amplitude of Ba2+ tail currents through open Ca channels at all voltages from -40 to +150 mV with a slight shift in the activation curve determined from the current-voltage (I-V) relationship for the tail currents. NE did not change the voltage dependence of the steady-state inactivation of the calcium channels. 5. NE inhibited Ca2+ current either in the absence or presence of nifedipine but to a lesser extent in the presence of omega-conotoxin (omega-CGTX), suggesting that the Ca channels inhibited by NE are predominantly omega-CGTX sensitive. 6. The inhibition of ICa by NE was mimicked by the alpha 1-adrenergic agonists methoxamine and phenylephrine and potentiated in the presence of the alpha 2-adrenoceptor antagonist yohimbine (10 microM). NE inhibition of ICa was antagonized by bath application of the alpha-adrenergic antagonist phentolamine (1 microM), but not by prazosin (1-10 microM), yohimbine, or the beta-adrenergic antagonist propranolol (1 microM). Taken together, these results suggest that NE inhibition of Ca2+ current in rat parasympathetic cardiac neurons is mediated by an alpha-adrenergic receptor with properties that may differ from alpha 1- and alpha 2-adrenoceptors. 7. In approximately 35% of neurons studied, NE not only reduced depolarization-activated inward Ca2+ current but also increased an outward current, with a shift of the I-V curve and reversal potential to more negative voltages.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Florida 33101.
authors.forename: Z J
authors.initials: ZJ
authors.lastname: Xu
authors.forename: D J
authors.initials: DJ
authors.lastname: Adams
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D004553:Electric Conductivity; D005724:Ganglia / Q000166:cytology / Q000502:physiology*; D006329:Heart Conduction System / Q000166:cytology / Q000502:physiology*; D007477:Ions; D009474:Neurons / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000166:cytology / Q000502:physiology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D015290:Second Messenger Systems; D020866:omega-Conotoxin GVIA
chemical_list: D000316:Adrenergic alpha-Agonists; D002121:Calcium Channel Blockers; D007477:Ions; D010456:Peptides, Cyclic; D011942:Receptors, Adrenergic, alpha; D020866:omega-Conotoxin GVIA; D002118:Calcium; D009638:Norepinephrine