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Cold Spring Harb Perspect Biol. 2017 May 1;9(5). pii: a027714. doi: 10.1101/cshperspect.a027714.

Membrane Currents, Gene Expression, and Circadian Clocks.

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Oregon Institute of Occupational Health Sciences and Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon 97239.
Department of Cellular and Molecular Physiology and Department of Genetics, Yale School of Medicine, New Haven, Connecticut 06520.
Department of Psychiatry & Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California 90024.


Neuronal circadian oscillators in the mammalian and Drosophila brain express a circadian clock comprised of interlocking gene transcription feedback loops. The genetic clock regulates the membrane electrical activity by poorly understood signaling pathways to generate a circadian pattern of action potential firing. During the day, Na+ channels contribute an excitatory drive for the spontaneous activity of circadian clock neurons. Multiple types of K+ channels regulate the action potential firing pattern and the nightly reduction in neuronal activity. The membrane electrical activity possibly signaling by changes in intracellular Ca2+ and cyclic adenosine monophosphate (cAMP) regulates the activity of the gene clock. A decline in the signaling pathways that link the gene clock and neural activity during aging and disease may weaken the circadian output and generate significant impacts on human health.

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