Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
Na(+) channels are often spliced but little is known about the functional consequences of splicing. We have been studying the regulation of Na(+) current inactivation in an electric fish model in which systematic variation in the rate of inactivation of the electric organ Na(+) current shapes the electric organ discharge (EOD), a sexually dimorphic, androgen-sensitive communication signal. Here, we examine the relationship between an Na(+) channel (Na(v)1.4b), which has two splice forms, and the waveform of the EOD. One splice form (Na(v)1.4bL) possesses a novel first exon that encodes a 51 aa N-terminal extension. This is the first report of an Na(+) channel with alternative splicing in the N terminal. This N terminal is present in zebrafish suggesting its general importance in regulating Na(+) currents in teleosts. The extended N terminal significantly speeds fast inactivation, shifts steady-state inactivation, and dramatically enhances recovery from inactivation, essentially fulfilling the functions of a beta subunit. Both splice forms are equally expressed in muscle in electric fish and zebrafish but Na(v)1.4bL is the dominant form in the electric organ implying electric organ-specific transcriptional regulation. Transcript abundance of Na(v)1.4bL in the electric organ is positively correlated with EOD frequency and lowered by androgens. Thus, shaping of the EOD waveform involves the androgenic regulation of a rapidly inactivating splice form of an Na(+) channel. Our results emphasize the role of splicing in the regulation of a vertebrate Na(+) channel and its contribution to a known behavior.
Akopian,
Trans-splicing of a voltage-gated sodium channel is regulated by nerve growth factor.
1999, Pubmed
Akopian,
Trans-splicing of a voltage-gated sodium channel is regulated by nerve growth factor.
1999,
Pubmed Becker,
Tissue-specific expression of a Drosophila calcium-activated potassium channel.
1995,
Pubmed Blumenstein,
A novel long N-terminal isoform of human L-type Ca2+ channel is up-regulated by protein kinase C.
2002,
Pubmed
,
Xenbase Bohm,
Transcriptional control of Ca(2+)-activated K(+) channel expression: identification of a second, evolutionarily conserved, neuronal promoter.
2000,
Pubmed Chew,
Regulation of ion channel expression in neural cells by hormones and growth factors.
1998,
Pubmed Chopra,
Molecular cloning and analysis of zebrafish voltage-gated sodium channel beta subunit genes: implications for the evolution of electrical signaling in vertebrates.
2007,
Pubmed Chou,
Prediction of protein conformation.
1974,
Pubmed Cormier,
Secondary structure of the human cardiac Na+ channel C terminus: evidence for a role of helical structures in modulation of channel inactivation.
2002,
Pubmed Dib-Hajj,
Insertion of a SNS-specific tetrapeptide in S3-S4 linker of D4 accelerates recovery from inactivation of skeletal muscle voltage-gated Na channel mu1 in HEK293 cells.
1997,
Pubmed Dietrich,
Functional analysis of a voltage-gated sodium channel and its splice variant from rat dorsal root ganglia.
1998,
Pubmed
,
Xenbase Dobrzycka,
Estrogen receptor corepressors -- a role in human breast cancer?
2003,
Pubmed Du,
An alanine in segment 3 of domain III (IIIS3) of the cockroach sodium channel contributes to the low pyrethroid sensitivity of an alternative splice variant.
2006,
Pubmed Fein,
Cloning and expression of a zebrafish SCN1B ortholog and identification of a species-specific splice variant.
2007,
Pubmed
,
Xenbase Ferrari,
Individual variation in and androgen-modulation of the sodium current in electric organ.
1995,
Pubmed French,
Structural requirements for rapid inactivation and voltage dependence in splice variants of lobster Shaker potassium channels.
2005,
Pubmed
,
Xenbase Garnier,
Analysis of the accuracy and implications of simple methods for predicting the secondary structure of globular proteins.
1978,
Pubmed Hopkins,
Electric communication in the reproductive behavior of Sternopygus macrurus (Gymnotoidei).
1974,
Pubmed Kerr,
Novel isoforms of the sodium channels Nav1.8 and Nav1.5 are produced by a conserved mechanism in mouse and rat.
2004,
Pubmed Liman,
Subunit stoichiometry of a mammalian K+ channel determined by construction of multimeric cDNAs.
1992,
Pubmed
,
Xenbase Liu,
Individual variation and hormonal modulation of a sodium channel beta subunit in the electric organ correlate with variation in a social signal.
2007,
Pubmed
,
Xenbase Lopreato,
Evolution and divergence of sodium channel genes in vertebrates.
2001,
Pubmed Mantegazza,
Role of the C-terminal domain in inactivation of brain and cardiac sodium channels.
2001,
Pubmed Mattick,
The evolution of controlled multitasked gene networks: the role of introns and other noncoding RNAs in the development of complex organisms.
2001,
Pubmed McAnelly,
Coregulation of voltage-dependent kinetics of Na(+) and K(+) currents in electric organ.
2000,
Pubmed Mulley,
SCN1A mutations and epilepsy.
2005,
Pubmed Ou,
Tetrodotoxin-resistant Na+ channels in human neuroblastoma cells are encoded by new variants of Nav1.5/SCN5A.
2005,
Pubmed Plummer,
Alternative splicing of the sodium channel SCN8A predicts a truncated two-domain protein in fetal brain and non-neuronal cells.
1997,
Pubmed Priori,
Natural history of Brugada syndrome: insights for risk stratification and management.
2002,
Pubmed Raymond,
Expression of alternatively spliced sodium channel alpha-subunit genes. Unique splicing patterns are observed in dorsal root ganglia.
2004,
Pubmed Sarao,
Developmentally regulated alternative RNA splicing of rat brain sodium channel mRNAs.
1991,
Pubmed Schaller,
Alternatively spliced sodium channel transcripts in brain and muscle.
1992,
Pubmed Shang,
Tandem promoters and developmentally regulated 5'- and 3'-mRNA untranslated regions of the mouse Scn5a cardiac sodium channel.
2005,
Pubmed Stocker,
Alternative Shaker transcripts express either rapidly inactivating or noninactivating K+ channels.
1990,
Pubmed
,
Xenbase Sun,
Probing sodium channel cytoplasmic domain structure. Evidence for the interaction of the rSkM1 amino and carboxyl termini.
1995,
Pubmed Tateyama,
Modulation of cardiac sodium channel gating by protein kinase A can be altered by disease-linked mutation.
2003,
Pubmed Thackeray,
Conserved alternative splicing patterns and splicing signals in the Drosophila sodium channel gene para.
1995,
Pubmed Vinogradov,
Intron-genome size relationship on a large evolutionary scale.
1999,
Pubmed Walters,
Receptors for steroid hormones: membrane-associated and nuclear forms.
2004,
Pubmed Wang,
Molecular characterization of an arachnid sodium channel gene from the varroa mite (Varroa destructor).
2003,
Pubmed Zakon,
Sodium channel genes and the evolution of diversity in communication signals of electric fishes: convergent molecular evolution.
2006,
Pubmed Zhang,
A carboxy-terminal alpha-helical segment in the rat skeletal muscle voltage-dependent Na+ channel is responsible for its interaction with the amino-terminus.
2000,
Pubmed
