Abstract

Native rat lactotrophs express thyrotrophin-releasing hormone-dependent K⁺ currents consisting of fast and slow deactivating components that are both sensitive to the class III anti-arrhythmic drugs that block the eag-related gene (ERG) K⁺ current (I_ERG). Here we describe in MMQ prolactin-releasing pituitary cells the isolation of the slowly deactivating long-lasting component (I_ERGS), which, unlike the fast component (I_ERGF), is insensitive to verapamil 2 μm but sensitive to a novel scorpion toxin (ErgTx-2) that hardly affects I_ERGF. The time constants of I_ERGS activation, deactivation, and recovery from inactivation are more than one order of magnitude greater than in I_ERGF, and the voltage-dependent inactivation is left-shifted by ∼25 mV. The very slow MMQ firing frequency (∼0.2 Hz) investigated in perforated patch is increased approximately four times by anti-arrhythmic agents, by ErgTx-2, and by the abrupt I_ERGSdeactivation. Prolactin secretion in the presence of anti-arrhythmics is three- to fourfold higher in comparison with controls. We provide evidence from I_ERGS andI_ERGF simulations in a firing model cell to indicate that only I_ERGS has an accommodating role during the experimentally observed very slow firing. Thus, we suggest that I_ERGS potently modulates both firing and prolactin release in lactotroph cells.