Journal of Neuroscience, Vol 15, 449-457, Copyright © 1995 by Society for Neuroscience
Inhibition of voltage-gated K+ channel gene expression by the neuropeptide thyrotropin-releasing hormone
K Takimoto, R Gealy, AF Fomina, JS Trimmer and ES Levitan
Department of Pharmacology, University of Pittsburgh, Pennsylvania 15261.
Many neurotransmitters regulate action potential activity in neuronal,
endocrine, and cardiac cells by rapidly modulating the gating of K+
channels. Neurotransmitters might also produce prolonged effects on
excitability by regulating the expression of K+ channel genes. Here we show
that the neuropeptide thyrotropin-releasing hormone (TRH) down- regulates
Kv1.5 and Kv2.1 K+ channel mRNAs in clonal pituitary cells. The effect 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 12 hr. The
change in channel protein expression is associated with a decrease in
voltage-gated K+ currents. Thus, TRH enhances excitability by inhibiting K+
channel gene expression. Neuropeptide regulation of K+ channel gene
expression may produce long-term changes in neuronal action potential
activity and synaptic transmission.
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