Ionic mechanisms underlying TRH-induced prolactin secretion in rat lactotrophs.
Whole cell patch-clamp experiments were performed in clonal rat pituitary cells (GH3/B6 cells) to further analyze an inward-rectifying K current (IK, IR) which is suggested to be involved in the thyrotropin-releasing hormone (TRH)-induced increase in prolactin secretion from these cells. Using the class III antiarrhythmic agent E-4031 which is known as specific blocker of ether-á-go-go-related gene (ERG) K channels, the inward-rectifying K current could be isolated as the drug-sensitive current. To elucidate in molecular basis of this current, comparative experiments were performed in CHO cells which served as heterologous expression system for RERG, the rat homologue of the human ERG (HERG). It is shown that the inward-rectifying K current has properties identical to those mediated by channels encoded by RERG. In external 5 mM K+ solution, the ERG-like current IK, IR was an outward current in the physiological potential range, and this outward current could be strongly reduced by TRH. A specific block of IK, IR was able to mimick the second phase of the TRH-response which is characterized by a depolarization and/or by an increase in the frequency of Ca action potentials. These data show, that the ERG-like current in GH3/B6 cells contributes to the maintainance of the resting membrane potential and that it plays an important part in the mechanisms of the effects of TRH leading to an increase in prolactin secretion.
Schwarz
J R
JR
Abteilung für angewandte Physiologie, Universität Hamburg, Germany.
Bauer
C K
CK
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D016466:CHO Cells; D002460:Cell Line; D003001:Cloning, Molecular; D006224:Cricetinae; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology; D010902:Pituitary Gland / Q000378:metabolism*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D011388:Prolactin / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D013973:Thyrotropin-Releasing Hormone / Q000502:physiology*
D000889:Anti-Arrhythmia Agents; D010880:Piperidines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011725:Pyridines; C063968:E 4031; D013973:Thyrotropin-Releasing Hormone; D011388:Prolactin