Na+ currents that fail to inactivate

doi:10.1016/0166-2236(93)90077-Y

Trends in Neurosciences

Volume 16, Issue 11, November 1993, Pages 455-460

https://doi.org/10.1016/0166-2236(93)90077-Y Get rights and content

Abstract

Textbook accounts give the impression that Na⁺ channels are short-acting binary switches: depolarization opens them, but only for about one millisecond. In contrast to this simplified view, a small but significant fraction of the total Na⁺ current in neurons occurs because channels open after long delays or in long-duration bursts of openings. Such non-inactivating Na⁺ current acts physiologically in neurons to amplify synaptic potentials and enhance endogenous rhythmicity, and also to aid repetitive firing of action potentials. In glial cells it also may regulate Na⁺ −K⁺ ATPase activity. The evidence for non-inactivating Na⁺ current in a variety of neurons and glia is reviewed, along with a brief discussion of its ion channel substrate and its relevance for neurological diseases and drug therapy.

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Citation Excerpt :
The short intracellular loop connecting domains III and IV, known as the fast inactivation gate, serves as an intracellular blocking particle that occludes the pore during inactivation (Catterall, 2012). Besides the transient (i.e., fast inactivating) sodium currents (INaT), which are responsible for the upstroke of action potentials, there are also tetrodotoxin (TTX)-sensitive non-inactivating or persistent currents (INaP), which activate at subthreshold voltages and cannot inactivate completely even with prolonged depolarization (Taylor, 1993; Crill, 1996; Stafstrom, 2007; Kiss, 2008). INaP have been detected in numerous types of vertebrate neurons in the brain, such as the suprachiasmatic nucleus (Pennartz et al., 1997; Jackson et al., 2004); cerebellar nuclei (Raman et al., 2000); and tuberomammillary neurons (Llinas and Alonso, 1992; Uteshev et al., 1995; Taddese and Bean, 2002).
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Trends in Neurosciences

ReviewNa+ currents that fail to inactivate

Abstract

Brain Res.

Neuron

Neuron

Brain Res.

Neuron

Neuron

Trends Pharmacol. Sci.

J. Mol. Cell Cardiol.

Eur. J. Pharmacol.

Brain Res.

Exp. Neurol.

Neurosci. Lett.

Neuroscience

Neuroscience

Nature

J. Physiol.

J. Neurophysiol.

Nature

J. Physiol.

J. Gen. Physiol.

J. Neurosci.

J. Physiol.

J. Physiol.

J. Neurophysiol.

Review
Na⁺ currents that fail to inactivate