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Voltage-Gated Ion Channels

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Neuroscience in the 21st Century

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Abstract

Electrical signaling by ion channels is a fundamental cellular regulatory pathway in all organisms from prokaryotes to humans. Voltage-gated Na+ (VGSC), Ca2+ (VGCC), and K+ (VGPC) channels are responsible for action potential generation in electrically excitable cells, for example, neurons and muscle cells, and for regulation of membrane potential and intracellular Ca2+ levels in other cell types. The basic functional properties of this protein family were initially defined in classic voltage-clamp studies by Hodgkin and Huxley in 1952. During the 1970s, many scientists built upon the fundamental insights of these pioneers to investigate electrical signal transduction using patch-clamp techniques, to measure ion channel function by neurotoxin-activated ion flux, and to detect VGSC proteins (the first member of this family to be studied biochemically) by high affinity binding of the neurotoxins tetrodotoxin, saxitoxin, and scorpion toxin (discussed later in this chapter). However, the molecular basis of excitability remained unclear until the 1980s, when Dr. William A. Catterall and his colleagues at the University of Washington discovered the VGSC protein (in 1980) and the VGCC protein (in 1984).

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Abbreviations

BACE1:

β-site amyloid precursor protein-cleaving enzyme 1

Ca2+ :

Calcium

CAM:

Cell adhesion molecule

CaMKII:

Calcium/calmodulin-dependent protein kinase II

cDNA:

Complementary deoxyribonucleic acid

Cl− :

Chloride

CNS:

Central nervous system

ENa:

Sodium equilibrium potential

ERK:

Extracellular-signal regulated kinases

Ff:

Fraction of channels that inactivate through fast inactivation

FHF:

Fibroblast growth factor homologous factors

Fr:

Fraction of channels that have recovered from inactivation

Fs:

Fraction of channels that inactivate through slow inactivation

g:

Conductance

GEFS+ :

Genetic (generalized) epilepsy with febrile seizures plus

GPD1L:

Glycerol-3-phosphate dehydrogenase 1-like protein

I:

Current

ICD:

Intracellular domain

Ig:

Immunoglobulin

IP5P:

Inositol polyphosphate 5-phosphatase

Ipeak:

Peak current

iPSCs:

Induced pluripotent stem cells

K+ :

Potassium

MAPK:

Mitogen-activated protein kinases

MOG1:

Multicopy suppressor of gsp1

mRNA:

Messenger ribonucleic acid

Na+ :

Sodium

NF:

Neurofascin

Nr-CAM:

Neuronal cell adhesion molecule

PCR:

Polymerase chain reaction

PDZ:

Post synaptic density protein Drosophila disk large tumor suppressor, Zonula occludens-1 protein

PNS:

Peripheral nervous system

PP2A:

Protein phosphatase 2A

PTPH1:

Protein tyrosine phosphatase H1

REST:

RE1-silencing factor

RPTPβ:

Receptor phosphoprotein tyrosine phosphatase-β

Src:

Sarcoma

t:

Time

TM:

Transmembrane

tf:

Rate constant for fast inactivation

τr:

Rate constant for recovery

τs:

Rate constant for slow inactivation

TTX:

Tetrodotoxin

V:

Voltage

VGCC:

Voltage-gated calcium channels

VGPC:

Voltage-gated potassium channels

VGSC:

Voltage-gated sodium channels

Vm:

Membrane voltage membrane potential

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Authors and Affiliations

  1. Pharmacology, Molecular and Integrative Physiology, University of Michigan, 1150 W. Medical Center Dr, Ann Arbor, MI, 48109-5632, USA

    Lori Isom

  2. Neuroscience Program, Pharmacology, University of Michigan, Ann Arbor, MI, 48109, USA

    Gustavo Patino

  3. Pharmacology, University of Michigan, Ann Arbor, MI, USA

    Luis Lopez-Santiago & Yukun Yuan

Authors
  1. Lori Isom
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  2. Gustavo Patino
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  3. Luis Lopez-Santiago
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  4. Yukun Yuan
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Corresponding author

Correspondence to Lori Isom .

Editor information

Editors and Affiliations

  1. Laboratory of Neurobiology and Behavior, The Rockefeller University, New York, New York, USA

    Donald W. Pfaff

  2. National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH), Rockville, Maryland, USA

    Nora D. Volkow

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Isom, L., Patino, G., Lopez-Santiago, L., Yuan, Y. (2016). Voltage-Gated Ion Channels. In: Pfaff, D., Volkow, N. (eds) Neuroscience in the 21st Century. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-3474-4_3

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