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.
Inactivation determinants in segment IIIS6 of Ca(v)3.1.
Marksteiner R
,
Schurr P
,
Berjukow S
,
Margreiter E
,
Perez-Reyes E
,
Hering S
.
???displayArticle.abstract???
1. Low threshold, T-type, Ca(2+) channels of the Ca(v)3 family display the fastest inactivation kinetics among all voltage-gated Ca(2+) channels. The molecular inactivation determinants of this channel family are largely unknown. Here we investigate whether segment IIIS6 plays a role in Ca(v)3.1 inactivation as observed previously in high voltage-activated Ca(2+) channels. 2. Amino acids that are identical in IIIS6 segments of all Ca(2+) channel subtypes were mutated to alanine (F1505A, F1506A, N1509A, F1511A, V1512A, F1519A, FV1511/1512AA). Additionally M1510 was mutated to isoleucine and alanine. 3. The kinetic properties of the mutants were analysed with the two-microelectrode voltage-clamp technique after expression in Xenopus oocytes. The time constant for the barium current (I(Ba)) inactivation, tau(inact), of wild-type channels at -20 mV was 9.5 +/- 0.4 ms; the corresponding time constants of the mutants ranged from 9.2 +/- 0.4 ms in V1512A to 45.7 +/- 5.2 ms (4.8-fold slowing) in M1510I. Recovery at -80 mV was most significantly slowed by V1512A and accelerated by F1511A. 4. We conclude that amino acids M1510, F1511 and V1512 corresponding to previously identified inactivation determinants in IIIS6 of Ca(v)2.1 (Hering et al. 1998) have a significant role in Ca(v)3.1 inactivation. These data suggest common elements in the molecular architecture of the inactivation mechanism in high and low threshold Ca(2+) channels.
Berjukow,
Sequence differences between alpha1C and alpha1S Ca2+ channel subunits reveal structural determinants of a guarded and modulated benzothiazepine receptor.
1999, Pubmed
Berjukow,
Sequence differences between alpha1C and alpha1S Ca2+ channel subunits reveal structural determinants of a guarded and modulated benzothiazepine receptor.
1999,
Pubmed
Berjukow,
Amino acids in segment IVS6 and beta-subunit interaction support distinct conformational changes during Ca(v)2.1 inactivation.
2001,
Pubmed
,
Xenbase
Berjukow,
Molecular mechanism of calcium channel block by isradipine. Role of a drug-induced inactivated channel conformation.
2000,
Pubmed
,
Xenbase
Bourinet,
Splicing of alpha 1A subunit gene generates phenotypic variants of P- and Q-type calcium channels.
1999,
Pubmed
,
Xenbase
Cens,
Voltage and calcium use the same molecular determinants to inactivate calcium channels.
1999,
Pubmed
Chuang,
Inhibition of T-type voltage-gated calcium channels by a new scorpion toxin.
1998,
Pubmed
,
Xenbase
Doyle,
The structure of the potassium channel: molecular basis of K+ conduction and selectivity.
1998,
Pubmed
Ertel,
Nomenclature of voltage-gated calcium channels.
2000,
Pubmed
Grabner,
Transfer of 1,4-dihydropyridine sensitivity from L-type to class A (BI) calcium channels.
1996,
Pubmed
Hering,
Molecular mechanism of use-dependent calcium channel block by phenylalkylamines: role of inactivation.
1997,
Pubmed
,
Xenbase
Hering,
Ca2+ channel block and inactivation: common molecular determinants.
1998,
Pubmed
Hering,
Molecular determinants of inactivation in voltage-gated Ca2+ channels.
2000,
Pubmed
Herlitze,
Molecular determinants of inactivation and G protein modulation in the intracellular loop connecting domains I and II of the calcium channel alpha1A subunit.
1997,
Pubmed
Horton,
Engineering hybrid genes without the use of restriction enzymes: gene splicing by overlap extension.
1989,
Pubmed
Jen,
Calcium channelopathies in the central nervous system.
1999,
Pubmed
Kraus,
Molecular mechanism of diltiazem interaction with L-type Ca2+ channels.
1998,
Pubmed
,
Xenbase
Perez-Reyes,
Molecular characterization of a neuronal low-voltage-activated T-type calcium channel.
1998,
Pubmed
,
Xenbase
Perez-Reyes,
Molecular characterization of two members of the T-type calcium channel family.
1999,
Pubmed
,
Xenbase
Perozo,
Three-dimensional architecture and gating mechanism of a K+ channel studied by EPR spectroscopy.
1998,
Pubmed
Sokolov,
Modulation of slow inactivation in class A Ca2+ channels by beta-subunits.
2000,
Pubmed
,
Xenbase
Sokolov,
Inactivation determinant in the I-II loop of the Ca2+ channel alpha1-subunit and beta-subunit interaction affect sensitivity for the phenylalkylamine (-)gallopamil.
1999,
Pubmed
,
Xenbase
Soldatov,
Molecular determinants of L-type Ca2+ channel inactivation. Segment exchange analysis of the carboxyl-terminal cytoplasmic motif encoded by exons 40-42 of the human alpha1C subunit gene.
1998,
Pubmed
,
Xenbase
Spaetgens,
Multiple structural domains contribute to voltage-dependent inactivation of rat brain alpha(1E) calcium channels.
1999,
Pubmed
Staes,
The amino side of the C-terminus determines fast inactivation of the T-type calcium channel alpha1G.
2001,
Pubmed
Stephens,
The alpha1B Ca2+ channel amino terminus contributes determinants for beta subunit-mediated voltage-dependent inactivation properties.
2000,
Pubmed
Stotz,
Fast inactivation of voltage-dependent calcium channels. A hinged-lid mechanism?
2000,
Pubmed
Yarov-Yarovoy,
Molecular determinants of voltage-dependent gating and binding of pore-blocking drugs in transmembrane segment IIIS6 of the Na(+) channel alpha subunit.
2001,
Pubmed
,
Xenbase
Yellen,
The bacterial K+ channel structure and its implications for neuronal channels.
1999,
Pubmed
Zhang,
Molecular determinants of voltage-dependent inactivation in calcium channels.
1994,
Pubmed
,
Xenbase
