Membrane potential changes caused by thyrotropin-releasing hormone in the clonal GH3 cell and their relationship to secretion of pituitary hormone.

Effects of thyrotropin-releasing hormone (TRH; thyroliberin) on membrane electrical properties were studied in the clonal rat anterior pituitary cell (GH3) by continuous recording of the intracellular potential. Application of TRH, which stimulates the release of prolactin and growth hormone from the GH3 cell, elicited a transient hyperpolarization of the cell membrane followed by an enhancement of the generation of action potentials for an extended period in the majority of cells tested. The transient hyperpolarization was due to an increase of the membrane conductance to K+. The enhancement of the spike generation was not due to membrane depolarization. The input resistance of the cell membrane was found to be increased during the facilitation. Thus the mechanism of the facilitatory action of TRH is different from the mechanisms of conventional excitatory neurotransmitters. TRH enhances the spike generation, thus promoting Ca2+ entry from extra- to intracellular space (the action potential of the GH3 cell has a Ca2+ component) and stimulating the release of hormones. This notion is supported by the observation that cobalt ions, which block the calcium spike in these cells, completely abolished the stimulatory effect of TRH on the release of prolactin and growth hormone.