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
- Ï„f:
-
Rate constant for fast inactivation
- Ï„r:
-
Rate constant for recovery
- Ï„s:
-
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
Further Reading
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Catterall WA (1984) The molecular basis of neuronal excitability. Science 223:653–661
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Isom, L., Patino, G., Lopez-Santiago, L., Yuan, Y. (2013). Voltage-Gated Ion Channels. In: Pfaff, D.W. (eds) Neuroscience in the 21st Century. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-1997-6_3
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DOI: https://doi.org/10.1007/978-1-4614-1997-6_3
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-1996-9
Online ISBN: 978-1-4614-1997-6
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