Effect of catecholamines on the hyperpolarization-activated cationic Ih and the inwardly rectifying potassium I(Kir) currents in the rat substantia nigra pars compacta.
Whole-cell ruptured-patch and perforated-patch recordings were used in principal neurons of the rat substantia nigra pars compacta (SNc) to study the effect of catecholamines both on the hyperpolarization-activated cationic (Ih) and the inwardly rectifying potassium (I(Kir)) currents. In internal potassium, a 2 min bath application of noradrenaline (NA; 50 microM) or dopamine (DA; 50 microM) both inhibited Ih and induced an outward current associated with an increase in I(Kir) conductance. These two effects recovered poorly after wash-out. Protein kinase A (PKA), protein kinase C (PKC) and phosphatases 1 and 2A inhibitors did not modify the NA and DA effects on the amplitude of Ih and I(Kir) currents. They also had no effect on the recovery of the catecholamine responses. In perforated-patch experiments, NA and DA also induced an inhibition of Ih and revealed an outward current associated with an increase in conductance. However, both effects recovered in less than 5 min following the wash-out. These results indicate that neither PKA, PKC, nor phosphatases 1 or 2A were required in the NA and DA modulation of these two currents and that an intracellular factor, that could be either washed-out or inversely up-regulated in the ruptured-patch configuration, was implicated in the recovery of both effects. In the presence of external barium (300 microM) or internal caesium which both blocked the outward current and the increase in conductance, neither NA nor DA affected Ih, suggesting that the effect on Ih observed is secondary to the activation of the I(Kir) channels. Increasing chloride conductance of the cell by activation of GABA(A) receptors also induced an inhibition of Ih. All together these results suggest that the NA or DA induced inhibition of Ih could result from an occlusion of Ih by a space-clamp effect.
Laboratoire de Neurobiologie Cellulaire, Institut des Neurosciences, Université Pierre et Marie Curie, Paris, France. Laurence.Cathala@snv.jussieu.fr
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D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002412:Cations / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D004553:Electric Conductivity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000737:chemistry / Q000201:enzymology; D009638:Norepinephrine / Q000494:pharmacology*; D019319:Okadaic Acid / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D011493:Protein Kinase C / Q000378:metabolism; D054645:Protein Phosphatase 1; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D019311:Staurosporine / Q000494:pharmacology; D013378:Substantia Nigra / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D013566:Sympathomimetics / Q000494:pharmacology*; D017557:Ventral Tegmental Area / Q000737:chemistry / Q000166:cytology / Q000502:physiology
D002316:Cardiotonic Agents; D002412:Cations; D018491:Dopamine Agonists; D004791:Enzyme Inhibitors; D010726:Phosphodiesterase Inhibitors; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D013566:Sympathomimetics; D019319:Okadaic Acid; D019257:Quinpirole; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D019311:Staurosporine; D011188:Potassium; D015056:1-Methyl-3-isobutylxanthine; D004298:Dopamine; D009638:Norepinephrine