Effect of dopamine receptor stimulation on voltage-dependent fast-inactivating Na super(+) currents in medial prefrontal cortex (mPFC) pyramidal neurons in adult rats

Impaired working memory is a common feature of neuropsychiatric disorders. It is dependent on control of the medial prefrontal cortex (mPFC) neurons by dopamine. The purpose of this study was to test the effects of a D sub(1/5)-type dopamine receptor agonist (SKF 38393, 10 mu M) on the membrane potential and on voltage-dependent fast-inactivating Na super(+) currents in mPFC pyramidal neurons obtained from adult (9-week-old) rats. Treatment of the pyramidal neurons with SKF 38393 did not affect the membrane potential recorded with the perforated-patch method. When recordings were performed in cell-attached configuration, the application of SKF 38393 did not change the Na super(+) current amplitude and shifted the current-voltage relationship of the Na super(+) currents towards hyperpolarisation, thus resulting in an increase of the current amplitudes in response to suprathreshold depolarisations. Pretreatment of the cells with a D sub(1/5) receptor antagonist (SCH 23390, 10 mu M) abolished the effect of the D sub(1/5)-type receptors on Na super(+)currents. The effect of the D sub(1/5) agonist was replicated by treating the cells with a membrane-permeable analogue, cAMP (8-bromo-cAMP, 100 mu M), and the effect was blocked by treating the cells with a protein kinase A inhibitor, (H-89, 2 mu M). In recordings performed from mechanically and enzymatically dispersed pyramidal neurons in the whole-cell configuration, when the cell interior was dialysed with pipette solution, application of the D sub(1/5) agonist decreased the Na super(+) current amplitude without changing the current-voltage relationship. We conclude that in the mPFC pyramidal neurons in slices with an intact intracellular environment (recordings in the cell-attached configuration), the activation of D sub(1/5)dopamine receptors increases the fast-inactivating Na super(+) current availability in response to suprathreshold depolarisations. The maximum Na super(+) current amplitude was not changed. A cAMP/protein kinase A pathway was responsible for the signal transduction from the D sub(1/5) dopamine receptors to the Na super(+) channels.