Tissue distribution and functional expression of the human voltage-gated sodium channel β3 subunit

Stevens, Edward B.; Cox, Peter; Shah, Bhaval S.; Dixon, A. R.; Richardson, Peter J.; Pinnock, R.D.; Lee, Kevin

doi:10.1007/s004240000449

Cited by 32 publications

(17 citation statements)

References 40 publications

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“…An additional subunit, ␤ 3 , predominant during development (406), has been found that accelerates inactivation but less than ␤ 1 with which it is closely related (300). The distribution of ␤ 3 in human tissues and comparative amino acid sequences of ␤ 1 , ␤ 2 , and ␤ 3 is described in Stevens et al (426). Most recently, a novel disulfide-linked subunit, ␤ 4 , has been identified which shows similarities with ␤ 2 ; on coexpression it shifts the activation curve in the hyperpolarizing direction without affecting inactivation (516).…”

Section: Importance Of the ␤-Subunitsmentioning

confidence: 94%

Sodium Channel Inactivation: Molecular Determinants and Modulation

Ulbricht

2005

Physiological Reviews

271

222

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Voltage-gated sodium channels open (activate) when the membrane is depolarized and close on repolarization (deactivate) but also on continuing depolarization by a process termed inactivation, which leaves the channel refractory, i.e., unable to open again for a period of time. In the "classical" fast inactivation, this time is of the millisecond range, but it can last much longer (up to seconds) in a different slow type of inactivation. These two types of inactivation have different mechanisms located in different parts of the channel molecule: the fast inactivation at the cytoplasmic pore opening which can be closed by a hinged lid, the slow inactivation in other parts involving conformational changes of the pore. Fast inactivation is highly vulnerable and affected by many chemical agents, toxins, and proteolytic enzymes but also by the presence of beta-subunits of the channel molecule. Systematic studies of these modulating factors and of the effects of point mutations (experimental and in hereditary diseases) in the channel molecule have yielded a fairly consistent picture of the molecular background of fast inactivation, which for the slow inactivation is still lacking.

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Section: Importance Of the ␤-Subunitsmentioning

confidence: 94%

Sodium Channel Inactivation: Molecular Determinants and Modulation

Ulbricht

2005

Physiological Reviews

271

222

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“…The protein, Na v b3, is composed of an N-terminal extracellular Ig-like domain, a transmembrane domain and a C-terminal intracellular domain. Na v b3 is expressed in the brain, heart, lung, skeletal muscle, kidney, and pancreas [Stevens et al, 2001]. The SCN3B gene is a member of the gene family SCNB gene family [Meadows and Isom, 2005] described above under SCN1B.…”

Section: Brs7-mutations In Scn3bmentioning

confidence: 99%

The genetic basis of Brugada syndrome: A mutation update

et al. 2009

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Brugada syndrome (BrS) is a condition characterized by a distinct ST-segment elevation in the right precordial leads of the electrocardiogram and, clinically, by an increased risk of cardiac arrhythmia and sudden death. The condition predominantly exhibits an autosomal dominant pattern of inheritance with an average prevalence of 5:10,000 worldwide. Currently, more than 100 mutations in seven genes have been associated with BrS. Loss-of-function mutations in SCN5A, which encodes the a-subunit of the Na v 1.5 sodium ion channel conducting the depolarizing I Na current, causes 15-20% of BrS cases. A few mutations have been described in GPD1L, which encodes glycerol-3-phosphate dehydrogenase-1 like protein; CACNA1C, which encodes the a-subunit of the Ca v 1.2 ion channel conducting the depolarizing I L,Ca current; CACNB2, which encodes the stimulating b2-subunit of the Ca v 1.2 ion channel; SCN1B and SCN3B, which, in the heart, encodes b-subunits of the Na v 1.5 sodium ion channel, and KCNE3, which encodes the ancillary inhibitory b-subunit of several potassium channels including the Kv4.3 ion channel conducting the repolarizing potassium I to current. BrS exhibits variable expressivity, reduced penetrance, and ''mixed phenotypes,'' where families contain members with BrS as well as long QT syndrome, atrial fibrillation, short QT syndrome, conduction disease, or structural heart disease, have also been described.

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“…b1 and b3 are co-expressed in many tissues [17,18]. In the heart, b1 is expressed throughout both atria and ventricles, whereas b3 expression is limited to the ventricles and Purkinje fibers [9].…”

Section: Introductionmentioning

confidence: 99%

Modulation of Nav1.5 by ?1- and ?3-subunit co-expression in mammalian cells

Lenkowski

Lee

et al. 2004

Pflugers Arch - Eur J Physiol

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Cardiac sodium channels (Na(v)1.5) comprise a pore-forming alpha-subunit and auxiliary beta-subunits that modulate channel function. In the heart, beta1 is expressed throughout the atria and ventricles, whilst beta3 is present only in the ventricles and Purkinje fibers. In view of this expression pattern, we determined the effects of beta3 and beta1 co-expression alone, and in combination, on Na(v)1.5 stably expressed in Chinese hamster ovary cells. The current/voltage relationship was shifted -5 mV with either beta1 or beta3 co-expression alone and -10 mV with co-expression of both beta1 and beta3. In addition, beta3 and beta1/beta3 co-expression accelerated macroscopic current decay. There were significant hyperpolarizing shifts in equilibrium gating relationships with co-expression of beta1 and beta3 alone and in combination. Co-expression of beta1/beta3 together resulted in a greater hyperpolarizing shift in channel availability, and an increase in the slopes of equilibrium gating relationships. Co-expression of beta3 and beta1/beta3, but not beta1, slowed recovery from inactivation at -90 mV. Development of inactivation at -70 and -50 mV was accelerated by beta-subunit co-expression alone and in combination. beta-Subunit co-expression also reduced the late Na current measured at 200 ms. In conclusion, beta-subunits modulate Na(v)1.5 gating with important differences between co-expression of beta1 and beta3 alone and beta1/beta3 together.

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Tissue distribution and functional expression of the human voltage-gated sodium channel β3 subunit

Cited by 32 publications

References 40 publications

Sodium Channel Inactivation: Molecular Determinants and Modulation

Sodium Channel Inactivation: Molecular Determinants and Modulation

The genetic basis of Brugada syndrome: A mutation update

Modulation of Nav1.5 by ?1- and ?3-subunit co-expression in mammalian cells

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