Na+ channel β subunits: Overachievers of the ion channel family
Voltage gated Na+ channels (VGSCs) in mammals contain a pore-forming α subunit and one or more β subunits. There are five mammalian β subunits in total: β1, β1B, β2, β3, and β4, encoded by four genes: SCN1B-SCN4B. With the exception of the SCN1B splice variant, β1B, the β subunits are type I topolog...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2011-09-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fphar.2011.00053/full |
| _version_ | 1818138165689450496 |
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| author | William J Brackenbury Lori L Isom |
| author_facet | William J Brackenbury Lori L Isom |
| author_sort | William J Brackenbury |
| collection | DOAJ |
| description | Voltage gated Na+ channels (VGSCs) in mammals contain a pore-forming α subunit and one or more β subunits. There are five mammalian β subunits in total: β1, β1B, β2, β3, and β4, encoded by four genes: SCN1B-SCN4B. With the exception of the SCN1B splice variant, β1B, the β subunits are type I topology transmembrane proteins. In contrast, β1B lacks a transmembrane domain and is a secreted protein. A growing body of work shows that VGSC β subunits are multifunctional. While they do not form the ion channel pore, β subunits alter gating, voltage-dependence, and kinetics of VGSC α subunits and thus regulate cellular excitability in vivo. In addition to their roles in channel modulation, β subunits are members of the immunoglobulin (Ig) superfamily of cell adhesion molecules (CAMs) and regulate cell adhesion and migration. β subunits are also substrates for sequential proteolytic cleavage by secretases. An example of the multifunctional nature of β subunits is β1, encoded by SCN1B, that plays a critical role in neuronal migration and pathfinding during brain development, and whose function is dependent on Na+ current and γ-secretase activity. Functional deletion of SCN1B results in Dravet Syndrome, a severe and intractable pediatric epileptic encephalopathy. β subunits are emerging as key players in a wide variety of pathophysiologies, including epilepsy, cardiac arrhythmia, multiple sclerosis, Huntington’s disease, neuropsychiatric disorders, neuropathic and inflammatory pain, and cancer. β subunits mediate multiple signaling pathways on different timescales, regulating electrical excitability, adhesion, migration, pathfinding, and transcription. Importantly, some β subunit functions may operate independent of α subunits. Thus, β subunits perform critical roles during development and disease. As such, they may prove useful in disease diagnosis and therapy. |
| first_indexed | 2024-12-11T10:07:52Z |
| format | Article |
| id | doaj.art-af87fcc9469e4027a28f321e622250c8 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-11T10:07:52Z |
| publishDate | 2011-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-af87fcc9469e4027a28f321e622250c82022-12-22T01:11:52ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122011-09-01210.3389/fphar.2011.0005313746Na+ channel β subunits: Overachievers of the ion channel familyWilliam J Brackenbury0Lori L Isom1University of YorkUniversity of MichiganVoltage gated Na+ channels (VGSCs) in mammals contain a pore-forming α subunit and one or more β subunits. There are five mammalian β subunits in total: β1, β1B, β2, β3, and β4, encoded by four genes: SCN1B-SCN4B. With the exception of the SCN1B splice variant, β1B, the β subunits are type I topology transmembrane proteins. In contrast, β1B lacks a transmembrane domain and is a secreted protein. A growing body of work shows that VGSC β subunits are multifunctional. While they do not form the ion channel pore, β subunits alter gating, voltage-dependence, and kinetics of VGSC α subunits and thus regulate cellular excitability in vivo. In addition to their roles in channel modulation, β subunits are members of the immunoglobulin (Ig) superfamily of cell adhesion molecules (CAMs) and regulate cell adhesion and migration. β subunits are also substrates for sequential proteolytic cleavage by secretases. An example of the multifunctional nature of β subunits is β1, encoded by SCN1B, that plays a critical role in neuronal migration and pathfinding during brain development, and whose function is dependent on Na+ current and γ-secretase activity. Functional deletion of SCN1B results in Dravet Syndrome, a severe and intractable pediatric epileptic encephalopathy. β subunits are emerging as key players in a wide variety of pathophysiologies, including epilepsy, cardiac arrhythmia, multiple sclerosis, Huntington’s disease, neuropsychiatric disorders, neuropathic and inflammatory pain, and cancer. β subunits mediate multiple signaling pathways on different timescales, regulating electrical excitability, adhesion, migration, pathfinding, and transcription. Importantly, some β subunit functions may operate independent of α subunits. Thus, β subunits perform critical roles during development and disease. As such, they may prove useful in disease diagnosis and therapy.http://journal.frontiersin.org/Journal/10.3389/fphar.2011.00053/fulldevelopmentexcitabilityAdhesionbeta subunitvoltage-gated sodium channel |
| spellingShingle | William J Brackenbury Lori L Isom Na+ channel β subunits: Overachievers of the ion channel family Frontiers in Pharmacology development excitability Adhesion beta subunit voltage-gated sodium channel |
| title | Na+ channel β subunits: Overachievers of the ion channel family |
| title_full | Na+ channel β subunits: Overachievers of the ion channel family |
| title_fullStr | Na+ channel β subunits: Overachievers of the ion channel family |
| title_full_unstemmed | Na+ channel β subunits: Overachievers of the ion channel family |
| title_short | Na+ channel β subunits: Overachievers of the ion channel family |
| title_sort | na channel β subunits overachievers of the ion channel family |
| topic | development excitability Adhesion beta subunit voltage-gated sodium channel |
| url | http://journal.frontiersin.org/Journal/10.3389/fphar.2011.00053/full |
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