Peptide secretion from rat melanotropes is tonically inhibited by a dopaminergic synaptic input that develops after birth and acts through D2 dopamine receptors. In this study, whole-cell Na(+) currents were recorded from melanotropes that were isolated from rat pituitary intermediate lobes at postnatal days 1-20 (P1-P20) and maintained in culture for 5-24 h. Coincident with the development of innervation, melanotropes exhibited a progressive decrease in peak Na(+) current density from P3 to P14. The decrease involved a 50% reduction in maximal Na(+) conductance with no detectable changes in channel gating. Subcutaneous injections of the D2 antagonist sulpiride, applied from P11 to P13, restored melanotrope Na(+) channel activity to pre-innervation levels. Thus, the activation of D2 receptors by the dopaminergic input reduces the functional expression of Na(+) channels in melanotropes.