Effect of catecholamines on the hyperpolarization-activated cationic Ih and the inwardly rectifying potassium IKir 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 (I-h) and the inwardly rectifying potassium (I-Kir) currents. In internal potassium, a 2 min bath application of noradrenaline (NA; 50 mu M) or dopamine (DA; 50 mu M) both inhibited I-h and induced an outward current associated with an increase in I-Kir conductance. These two effects recovered poorly after washout. 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 I-h 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 I-h 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 or 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 mu M) or internal caesium which both blocked the outward current and the increase in conductance, neither NA nor DA affected I-h, suggesting that the effect on lh 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 I-h. All together these results suggest that the NA or DA induced inhibition of I-h could result from an occlusion of I-h by a space-clamp effect.