eNeuroJun 1, 2017

Reducing Kv4.1 Quickly Changes Nerve Cell Firing, Daily Clock Gene Activity, and Movement Rhythms

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Updated Mar 20, 2026

Abstract

Knockdown of in mouse neurons significantly increased repetitive firing rates during the day (6.4 ± 0.5 Hz) and night (4.3 ± 0.6 Hz).

Repetitive firing rates in Kv4.1-targeted neurons were notably higher compared to nontargeted neurons (day: 3.1 ± 0.5 Hz; night: 1.6 ± 0.3 Hz).
The current (I) was significantly reduced in Kv4.1-targeted neurons (day: 80.3 ± 11.8 pA/pF; night: 55.3 ± 7.7 pA/pF) compared to nontargeted neurons (day: 121.7 ± 10.2 pA/pF; night: 120.6 ± 16.5 pA/pF).
The effects of Kv4.1 knockdown on firing rates and current were more pronounced at night.
Nighttime input resistance increased significantly to 2256 ± 166 MΩ in Kv4.1-targeted neurons, versus 1143 ± 93 MΩ in nontargeted neurons.
Acute knockdown of Kv4.1 also shortened the circadian period of spontaneous electrical activity, clock gene expression, and locomotor activity by approximately 0.5 hours.

Simplified

Rapidly activating and inactivating A-type Kcurrents (I) encoded by Kv4.2 and Kv4.3 pore-forming (α) subunits of the Kv4 subfamily are key regulators of neuronal excitability. Previous studies have suggested a role for α-subunits in regulating the firing properties of mouse (SCN) neurons. To test this, we utilized an RNA-interference strategy to knockdown Kv4.1, acutely and selectively, in the SCN. Current-clamp recordings revealed that theknockdown of Kv4.1 significantly (< 0.0001) increased mean ± SEM repetitive firing rates in SCN neurons during the day (6.4 ± 0.5 Hz) and at night (4.3 ± 0.6 Hz), compared with nontargeted shRNA-expressing SCN neurons (day: 3.1 ± 0.5 Hz; night: 1.6 ± 0.3 Hz). Iwas also significantly (< 0.05) reduced in Kv4.1-targeted shRNA-expressing SCN neurons (day: 80.3 ± 11.8 pA/pF; night: 55.3 ± 7.7 pA/pF), compared with nontargeted shRNA-expressing (day: 121.7 ± 10.2 pA/pF; night: 120.6 ± 16.5 pA/pF) SCN neurons. The magnitude of the effect of Kv4.1-targeted shRNA expression on firing rates and Iwas larger at night. In addition, Kv4.1-targeted shRNA expression significantly (< 0.001) increased mean ± SEM nighttime input resistance (R; 2256 ± 166 MΩ), compared to nontargeted shRNA-expressing SCN neurons (1143 ± 93 MΩ). Additional experiments revealed that acute knockdown of Kv4.1 significantly (< 0.01) shortened, by ∼0.5 h, the circadian period of spontaneous electrical activity, clock gene expression and locomotor activity demonstrating a physiological role for Kv4.1-encoded Ichannels in regulating circadian rhythms in neuronal excitability and behavior. + A A A in A in vivo p p p p

Key numbers

6.4 ± 0.5 Hz

Increase in Repetitive Firing Rate

Mean firing rate in -targeted neurons during the day

2256 ± 166 MΩ

Input Resistance Increase

Nighttime input resistance in -targeted neurons

0.5 h

Circadian Period Shortening

Reduction in circadian period of electrical activity due to knockdown

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Reducing Kv4.1 Quickly Changes Nerve Cell Firing, Daily Clock Gene Activity, and Movement Rhythms

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