IA Channels Encoded by Kv1.4 and Kv4.2 Regulate Neuronal Firing in the Suprachiasmatic Nucleus and Circadian Rhythms in Locomotor Activity

Jul 21, 2012The Journal of neuroscience : the official journal of the Society for Neuroscience

Ion channels controlling nerve cell firing in the brain’s circadian clock and daily activity rhythms

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Mice lacking Kv1.4 or Kv4.2 channels exhibit 0.5-hour shorter periods of locomotor activity compared to wild-type mice.

SCN neurons in Kv1.4(-/-) and Kv4.2(-/-) mice demonstrate circadian rhythms in firing, but with 0.5-hour shorter periods than wild-type neurons.
Kv4.3(-/-) mice show wheel-running activity and SCN firing periods that are similar to wild-type animals, indicating that Kv4.3 may not play a critical role.
All three Kv channel α subunits are continuously expressed in the SCN throughout the day and night.
Kv1.4 and Kv4.2 channels are associated with regulating the excitability of SCN neurons, influencing circadian rhythms in behavior and firing patterns.

AI simplified

Neurons in the suprachiasmatic nucleus (SCN) display coordinated circadian changes in electrical activity that are critical for daily rhythms in physiology, metabolism, and behavior. SCN neurons depolarize spontaneously and fire repetitively during the day and hyperpolarize, drastically reducing firing rates, at night. To explore the hypothesis that rapidly activating and inactivating A-type (I(A)) voltage-gated K(+) (Kv) channels, which are also active at subthreshold membrane potentials, are critical regulators of the excitability of SCN neurons, we examined locomotor activity and SCN firing in mice lacking Kv1.4 (Kv1.4(-/-)), Kv4.2 (Kv4.2(-/-)), or Kv4.3 (Kv4.3(-/-)), the pore-forming (α) subunits of I(A) channels. Mice lacking either Kv1.4 or Kv4.2 α subunits have markedly shorter (0.5 h) periods of locomotor activity than wild-type (WT) mice. In vitro extracellular multi-electrode recordings revealed that Kv1.4(-/-) and Kv4.2(-/-) SCN neurons display circadian rhythms in repetitive firing, but with shorter periods (0.5 h) than WT cells. In contrast, the periods of wheel-running activity in Kv4.3(-/-) mice and firing in Kv4.3(-/-) SCN neurons were indistinguishable from WT animals and neurons. Quantitative real-time PCR revealed that the transcripts encoding all three Kv channel α subunits, Kv1.4, Kv4.2, and Kv4.3, are expressed constitutively throughout the day and night in the SCN. Together, these results demonstrate that Kv1.4- and Kv4.2-encoded I(A) channels regulate the intrinsic excitability of SCN neurons during the day and night and determine the period and amplitude of circadian rhythms in SCN neuron firing and locomotor behavior.

Full Text

Full text is available at the source.

View full text ↗

IA Channels Encoded by Kv1.4 and Kv4.2 Regulate Neuronal Firing in the Suprachiasmatic Nucleus and Circadian Rhythms in Locomotor Activity

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief