INHIBITION OF VOLTAGE-GATED K-EXPRESSION BY THE NEUROPEPTIDE THYROTROPIN-RELEASING-HORMONE( CHANNEL GENE)

Many neurotransmitters regulate action potential activity in neuronal, endocrine, and cardiac cells by rapidly modulating the gating of K+ c hannels. Neurotransmitters might also produce prolonged effects on exc itability by regulating the expression of K+ channel genes. Here we sh ow that the neuropeptide thyrotropin-releasing hormone (TRH) downregul ates Kv1.5 and Kv2.1 K+ channel mRNAs in clonal pituitary cells, The e ffect on Kv1.5 mRNA expression does not require protein synthesis and is due to decreased transcription. Immunoblots demonstrate that Kv1.5 and Kv2.1 immunoreactivities are significantly reduced by TRH within 1 2 hr. The change in channel protein expression is associated with a de crease in voltage-gated K+ currents. Thus, TRH enhances excitability b y inhibiting K+ channel gene expression. Neuropeptide regulation of K channel gene expression may produce long-term changes in neuronal act ion potential activity and synaptic transmission.