title: Effect of dopamine receptor stimulation on voltage-dependent fast-inactivating Na(+) currents in medial prefrontal cortex (mPFC) pyramidal neurons in adult rats.
abstract: 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 D1/5-type dopamine receptor agonist (SKF 38393, 10 microM) on the membrane potential and on voltage-dependent fast-inactivating Na+ 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 cellattached configuration, the application of SKF 38393 did not change the Na+ current amplitude and shifted the currentvoltage relationship of the Na+ currents towards hyperpolarisation, thus resulting in an increase of the current amplitudes in response to suprathreshold depolarisations. Pretreatment of the cells with a D1/5 receptor antagonist (SCH 23390, 10 microM) abolished the effect of the D1/5-type receptors on Na+ currents. The effect of the D1/5 agonist was replicated by treating the cells with a membrane-permeable analogue, cAMP (8-bromo-cAMP, 100 microM), and the effect was blocked by treating the cells with a protein kinase A inhibitor, (H-89, 2 microM). 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 D1/5 agonist decreased the Na+ 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 D1/5 dopamine receptors increases the fast-inactivating Na+ current availability in response to suprathreshold depolarisations. The maximum Na+ current amplitude was not changed. A cAMP/protein kinase A pathway was responsible for the signal transduction from the D1/5 dopamine receptors to the Na+ channels.
authors: Department of Physiology and Pathophysiology, Medical University of Warsaw, Warsaw, Poland.
authors: Bartlomiej
authors: B
authors: Szulczyk
authors: Aneta
authors: A
authors: Książek
authors: Wioleta
authors: W
authors: Ładno
authors: Pawel
authors: P
authors: Szulczyk
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D055592:Biophysical Phenomena / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D015259:Dopamine Agents / Q000494:pharmacology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000166:cytology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011954:Receptors, Dopamine / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism*
chemical_list: D015259:Dopamine Agents; D011954:Receptors, Dopamine; D026941:Sodium Channel Blockers; D061566:Voltage-Gated Sodium Channels; D015124:8-Bromo Cyclic Adenosine Monophosphate; D013779:Tetrodotoxin