Effect of catecholamines on the hyperpolarization-activated cationic I-h 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 prin cipal neurons of the rat substantia nigra pars compacta (SNc) to study the effect of catecholamines both on the hyperpolarization-activated cationic ( I-h) and the inwardly rectifying potassium (I-Kir) currents. In internal po tassium, a 2 min bath application of noradrenaline (NA; 50 mu M) or dopamin e (DA; 50 mu M) both inhibited I-h and induced an outward current associate d with an increase in I-Kir conductance. These two effects recovered poorly after washout. Protein kinase A (PKA), protein kinase C (PKC) and phosphat ases 1 and 2A inhibitors did not modify the NA and DA effects on the amplit ude of I-h and I-Kir currents. They also had no effect on the recovery of t he catecholamine responses. In perforated-patch experiments, NA and DA also induced an inhibition of I-h and revealed an outward current associated wi th 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 or the se two currents and that an intracellular factor, that could be either wash ed-out or inversely up-regulated in the ruptured-patch configuration, was i mplicated in the recovery of both effects. In the presence of external bari um (300 mu M) or internal caesium which both blocked the outward current an d the increase in conductance, neither NA nor DA affected I-h, suggesting t hat the effect on lh observed is secondary to the activation of the I-Kir c hannels. Increasing chloride conductance of the cell by activation of GABA( A) receptors also induced an inhibition of I-h. All together these results suggest that the NA or DA induced inhibition of I-h could result from an oc clusion of I-h by a space-clamp effect.