The erg inwardly rectifying K+ current and its modulation by thyrotrophin-releasing hormone in giant clonal rat anterior pituitary

1. The voltage-dependent inwardly rectifying K+ current (I-K,I-IR) of clonal rat anterior pituitary cells (GH(3)/B-6) was investigated in solutions with physiological K+ gradient using giant polynuclear cells. 2. I-K,I-IR was isolated by the use of the selective erg (ether-a-go-go-related gene) channel blocker E-4031. In external 5 mM K- solution, I-K,I-IR carried steady-state outward current in the potential range between -60 and 0 mV, with a maximum current amplitude at -40 mV. Negative to the K+ equilibrium potential, E-K, large transient inward currents occurred. 3. A selective pharmacological block of I-K,I-IR induced a sustained depolarization of the membrane potential when Ca2+ action potentials were blocked, confirming the contribution of I-K,I-IR to the resting membrane potential of GH(3)/B-6 cells. 4. Thyrotrophin-releasing hormone (TRH) reduced effectively the sustained outward and the transient inward I-K,I-IR. The magnitude of a TRH-induced depolarization of the membrane potential was consistent with an almost complete reduction of I-K,I-IR. 5. The results demonstrate that the TRH-induced reduction of I-K,I-IR is able to mediate the resting potential depolarization, suggesting; that the increase in the frequency of action potentials occurring during the second phase of the TRK response in GH cells should be sustained by I-K,I-IR inhibition. Moreover, this is the first evidence of a ligand-induced physiological modulation of an erg-mediated current.