Isolation of a Long-Lasting eag-Related Gene-Type K+ Current in MMQ Lactotrophs and Its Accommodating Role during Slow Firing and Prolactin Release

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 (IERG). Here we describe in MMQ prolactin-releasing pituitary cells the isolation of the slowly deactivating long-lasting component (IERGS), which, unlike the fast component (IERGF), is insensitive to verapamil 2 μm but sensitive to a novel scorpion toxin (ErgTx-2) that hardly affects IERGF. The time constants of IERGS activation, deactivation, and recovery from inactivation are more than one order of magnitude greater than in IERGF, 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 IERGSdeactivation. Prolactin secretion in the presence of anti-arrhythmics is three- to fourfold higher in comparison with controls. We provide evidence from IERGS andIERGF simulations in a firing model cell to indicate that only IERGS has an accommodating role during the experimentally observed very slow firing. Thus, we suggest that IERGS potently modulates both firing and prolactin release in lactotroph cells.

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