Auxiliary subunits of voltage-gated ion channels

Isom, Lori L.; Jongh, Karen S. De; Catterall, William A.

doi:10.1016/0896-6273(94)90436-7

Cited by 523 publications

(332 citation statements)

References 120 publications

Supporting

Mentioning

326

Contrasting

Unclassified

Order By: Relevance

“…The biophysical properties of heterologously expressed eq subunits depend on the auxiliary subunits coexpressed, particularly the 13 sub- units [39]. The phenotypic expression of Ca 2+ channels is thus a complex function of the cell's metabolic status, molecular repertoire, and specific isoforms being transcribed and translated [40].…”

Section: Resultsmentioning

confidence: 99%

T‐type Ca²⁺ channels and α_1E expression in spermatogenic cells, and their possible relevance to the sperm acrosome reaction

Liévano¹,

Santi

Serrano³

et al. 1996

FEBS Letters

160

153

View full text Add to dashboard Cite

There is pharmacological evidence that Ca 2+ channels play an essential role in triggering the mammalian sperm acrosome reaction, an exocytotic process required for sperm to fertilize the egg. Spermatozoa are small terminally differentiated cells that are difficult to study by conventional electrophysiological techniques. To identify the members of the voltagedependent Ca z+ channel family possibly present in sperm, we have looked for the expression of the a~A, tXlB, ale, atD and a~E genes in mouse testis and in purified spermatogenic cell populations with RT-PCR. Our results indicate that all 5 genes are expressed in mouse testis, and in contrast only alE, and to a minor extent CqA, are expressed in spermatogenic cells. In agreement with these findings, only T-type Ca 2+ channels sensitive to the dihydropyridine nifedipine were observed in patch-clamp recordings of pachytene s permatocytes. These 2+ results suggest that low-threshold Ca channels are the dihydropyridine-sensitive channels involved in the sperm acrosome reaction.

show abstract

Section: Resultsmentioning

confidence: 99%

T‐type Ca²⁺ channels and α_1E expression in spermatogenic cells, and their possible relevance to the sperm acrosome reaction

Liévano¹,

Santi

Serrano³

et al. 1996

FEBS Letters

160

153

View full text Add to dashboard Cite

show abstract

“…The higher sodium channel expression levels in neurons may partly account for these differences in the efficacies of veratridine and PbTx-2 [25]. Whereas neurons and HEK cells [26] express sodium channel β-subunits, CHL 1610 cells do not [27]. Sodium channel β-subunits regulate sodium channel α-subunit function at multiple levels including mRNA expression, channel stabilization/trafficking and direct channel modulation [28].…”

Section: Discussionmentioning

confidence: 99%

Antillatoxin is a sodium channel activator that displays unique efficacy in heterologously expressed rNav1.2, rNav1.4 and rNav1.5 alpha subunits

2010

View full text Add to dashboard Cite

BackgroundAntillatoxin (ATX) is a structurally unique lipopeptide produced by the marine cyanobacterium Lyngbya majuscula. ATX activates voltage-gated sodium channel α-subunits at an undefined recognition site and stimulates sodium influx in neurons. However, the pharmacological properties and selectivity of ATX on the sodium channel α-subunits were not fully characterized.ResultsIn this study, we characterized the pharmacological properties and selectivity of ATX in cells heterologously expressing rNav1.2, rNav1.4 or rNav1.5 α-subunits by using the Na+ selective fluorescent dye, sodium-binding benzofuran isophthalate. ATX produced sodium influx in cells expressing each sodium channel α-subunit, whereas two other sodium channel activators, veratridine and brevetoxin-2, were without effect. The ATX potency at rNav1.2, rNav1.4 and rNav1.5 did not differ significantly. Similarly, there were no significant differences in the efficacy for ATX-induced sodium influx between rNav1.2, rNav1.4 and rNav1.5 α-subunits. ATX also produced robust Ca2+ influx relative to other sodium channel activators in the calcium-permeable DEAA mutant of rNav1.4 α-subunit. Finally, we demonstrated that the 8-demethyl-8,9-dihydro-antillatoxin analog was less efficacious and less potent in stimulating sodium influx.ConclusionsATX displayed a unique efficacy with respect to stimulation of sodium influx in cells expressing rNav1.2, rNav1.4 and rNav1.5 α-subunits. The efficacy of ATX was distinctive inasmuch as it was not shared by activators of neurotoxin sites 2 and 5 on VGSC α-subunits. Given the unique pharmacological properties of ATX interaction with sodium channel α-subunits, decoding the molecular determinants and mechanism of action of antillatoxin may provide further insight into sodium channel gating mechanisms.

show abstract

“…113 Thus, the voltage-gated K ϩ channels have intracellular ␤ subunits (␤1-␤3) that bind to the ␣ subunits in a symmetrical fashion forming an octameric channel. The N-terminal of the ␤ subunits acts as an inactivation gate for the K v 1 ␣ subunits.…”

Section: Voltage-gated Potassium Channelsmentioning

confidence: 99%

Molecular Targets for Antiepileptic Drug Development

2007

View full text Add to dashboard Cite

Summary:This review considers how recent advances in the physiology of ion channels and other potential molecular targets, in conjunction with new information on the genetics of idiopathic epilepsies, can be applied to the search for improved antiepileptic drugs (AEDs). Marketed AEDs predominantly target voltage-gated cation channels (the ␣ subunits of voltagegated Na ϩ channels and also T-type voltage-gated Ca 2ϩ channels) or influence GABA-mediated inhibition. Recently, ␣2-␦ voltage-gated Ca 2ϩ channel subunits and the SV2A synaptic vesicle protein have been recognized as likely targets. Genetic studies of familial idiopathic epilepsies have identified numerous genes associated with diverse epilepsy syndromes, including genes encoding Na ϩ channels and GABA A receptors, which are known AED targets. A strategy based on genes associated with epilepsy in animal models and humans suggests other potential AED targets, including various voltage-gated Ca 2ϩ channel subunits and auxiliary proteins, A-or M-type voltage-gated K ϩ channels, and ionotropic glutamate receptors. Recent progress in ion channel research brought about by molecular cloning of the channel subunit proteins and studies in epilepsy models suggest additional targets, including G-protein-coupled receptors, such as GABA B and metabotropic glutamate receptors; hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channel subunits, responsible for hyperpolarization-activated current I h ; connexins, which make up gap junctions; and neurotransmitter transporters, particularly plasma membrane and vesicular transporters for GABA and glutamate. New information from the structural characterization of ion channels, along with better understanding of ion channel function, may allow for more selective targeting. For example, Na ϩ channels underlying persistent Na ϩ currents or GABA A receptor isoforms responsible for tonic (extrasynaptic) currents represent attractive targets. The growing understanding of the pathophysiology of epilepsy and the structural and functional characterization of the molecular targets provide many opportunities to create improved epilepsy therapies.

show abstract

Auxiliary subunits of voltage-gated ion channels

Cited by 523 publications

References 120 publications

T‐type Ca²⁺ channels and α_1E expression in spermatogenic cells, and their possible relevance to the sperm acrosome reaction

T‐type Ca²⁺ channels and α_1E expression in spermatogenic cells, and their possible relevance to the sperm acrosome reaction

Antillatoxin is a sodium channel activator that displays unique efficacy in heterologously expressed rNav1.2, rNav1.4 and rNav1.5 alpha subunits

Molecular Targets for Antiepileptic Drug Development

Contact Info

Product

Resources

About

Auxiliary subunits of voltage-gated ion channels

Cited by 523 publications

References 120 publications

T‐type Ca2+ channels and α1E expression in spermatogenic cells, and their possible relevance to the sperm acrosome reaction

T‐type Ca2+ channels and α1E expression in spermatogenic cells, and their possible relevance to the sperm acrosome reaction

Antillatoxin is a sodium channel activator that displays unique efficacy in heterologously expressed rNav1.2, rNav1.4 and rNav1.5 alpha subunits

Molecular Targets for Antiepileptic Drug Development

Contact Info

Product

Resources

About

T‐type Ca²⁺ channels and α_1E expression in spermatogenic cells, and their possible relevance to the sperm acrosome reaction

T‐type Ca²⁺ channels and α_1E expression in spermatogenic cells, and their possible relevance to the sperm acrosome reaction