An inward‐rectifying K+ current in clonal rat pituitary cells and its modulation by thyrotrophin‐releasing hormone.

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Abstract
1. Voltage‐dependent K+ currents were recorded in cultured tumour‐derived anterior pituitary cells of the rat (GH3 cells) with the patch clamp technique. An inward‐rectifying current is described which is found to be carried by K+. 2. In isotonic KCl, whole‐cell inward K+ currents were elicited by hyperpolarizing pulses from a holding potential of ‐40 mV. These inward K+ currents showed time‐ and voltage‐dependent inactivation at potentials more negative than ‐60 mV. Inactivation was faster and more complete at larger hyperpolarizations. Recovery from inactivation was also time‐ and voltage‐dependent. It was faster and more complete with more positive potentials. Time course of inactivation and of recovery from inactivation could be fitted by single exponentials. 3. Two results showed that a steady inward K+ current is present at ‐40 mV. The holding current at ‐40 mV was reduced following complete inactivation of the inward K+ current during strong hyperpolarizing pulses, and the amplitude of maximum inward K+ current elicited by hyperpolarization increased after depolarizing pre‐pulses of 5 s. The resting conductance was estimated to be 20‐30% of the maximum inward‐rectifying conductance. 4. The inward K+ current was drastically reduced by Cs+ and Ba2+, but not by Ni2+ and Co2+. Quinidine, 4‐aminopyridine and tetraethylammonium chloride blocked the current. In contrast, dendrotoxin was without effect. 5. Thyrotrophin‐releasing hormone (TRH) which induces biphasic secretion of prolactin in GH3 cells consistently reduced the inward K+ current in the presence of internal Ca2+. This reduction was abolished if the pipette solution contained guanosine 5'‐O‐(2‐thiodiphosphate) (GDP beta S; 400 microM), confirming the involvement of G‐proteins in the signal transduction pathway. 6. TRH shifted the voltage‐dependence of inward K+ current inactivation to less negative potentials resulting in pronounced K+ current inactivation in the range of the resting potential of these cells (‐40 to ‐60 mV). 7. In intact cells, closing of K+ channels would result in a depolarization. The existence of an inward‐rectifying K+ current in GH3 cells which is able to be reduced by TRH could readily explain the TRH‐induced increase in action potential firing underlying the sustained second phase of secretion.

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