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 determinant in the I-II loop of the Ca2+ channel alpha1-subunit and beta-subunit interaction affect sensitivity for the phenylalkylamine (-)gallopamil.
Sokolov S
,
Weiss RG
,
Kurka B
,
Gapp F
,
Hering S
.
???displayArticle.abstract???
1. The role of calcium (Ca2+) channel inactivation in the molecular mechanism of channel block by phenylalkylamines (PAAs) was analysed in a PAA-sensitive rabbit brain class A Ca2+ channel mutant (alpha1A-PAA). Use-dependent barium current (IBa) inhibition of alpha1A-PAA by (-)gallopamil and Ca2+ channel recovery from inactivation and block were studied with two-microlectrode voltage clamp after expression of alpha1A-PAA and auxiliary alpha2-delta- and beta1a- or beta2a-subunits in Xenopus oocytes. 2. Mutation Arg387Glu (alpha1A numbering) in the intracellular loop connecting domains I and II of alpha1A-PAA slowed the inactivation kinetics and reduced use-dependent inhibition (100 ms test pulses at 0.2 Hz from -80 to 20 mV) of the resulting mutant alpha1A-PAA/R-E/beta1a channels by 100 microM (-)gallopamil (53 +/- 2 %, alpha1A-PAA/beta1a vs. 31 +/- 2 %, alpha1A-PAA/R-E/beta1a, n >= 4). This amino acid substitution simultaneously accelerated the recovery of channels from inactivation and from block by (-)gallopamil. 3. Coexpression of alpha1A-PAA with the beta2a-subunit reduced fast IBa inactivation and induced a substantial reduction in use-dependent IBa inhibition by (-)gallopamil (25 +/- 4 %, alpha1A-PAA/beta2a; 13 +/- 1 %, alpha1A-PAA/R-E/beta2a). The time constant of recovery from block at rest was not significantly affected. 4. These results demonstrate that changes in channel inactivation induced by Arg387Glu or beta2a-alpha1-subunit interaction affect the drug-channel interaction.
Aczél,
Mechanism of voltage- and use-dependent block of class A Ca2+ channels by mibefradil.
1998, Pubmed,
Xenbase
Aczél,
Mechanism of voltage- and use-dependent block of class A Ca2+ channels by mibefradil.
1998,
Pubmed
,
Xenbase
Berjukow,
Sequence differences between alpha1C and alpha1S Ca2+ channel subunits reveal structural determinants of a guarded and modulated benzothiazepine receptor.
1999,
Pubmed
Bezprozvanny,
Voltage-dependent blockade of diverse types of voltage-gated Ca2+ channels expressed in Xenopus oocytes by the Ca2+ channel antagonist mibefradil (Ro 40-5967).
1995,
Pubmed
,
Xenbase
Bourinet,
Splicing of alpha 1A subunit gene generates phenotypic variants of P- and Q-type calcium channels.
1999,
Pubmed
,
Xenbase
Boyett,
Ultra-slow voltage-dependent inactivation of the calcium current in guinea-pig and ferret ventricular myocytes.
1994,
Pubmed
Degtiar,
Calcium channel block by (-)devapamil is affected by the sequence environment and composition of the phenylalkylamine receptor site.
1997,
Pubmed
,
Xenbase
Grabner,
Transfer of 1,4-dihydropyridine sensitivity from L-type to class A (BI) calcium channels.
1996,
Pubmed
Hering,
Transfer of high sensitivity for benzothiazepines from L-type to class A (BI) calcium channels.
1996,
Pubmed
,
Xenbase
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
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
Hockerman,
Molecular determinants of drug binding and action on L-type calcium channels.
1997,
Pubmed
Hockerman,
Molecular determinants of high affinity phenylalkylamine block of L-type calcium channels in transmembrane segment IIIS6 and the pore region of the alpha1 subunit.
1997,
Pubmed
Hockerman,
Molecular determinants of high affinity phenylalkylamine block of L-type calcium channels.
1995,
Pubmed
Hondeghem,
Antiarrhythmic agents: the modulated receptor mechanism of action of sodium and calcium channel-blocking drugs.
1984,
Pubmed
Horton,
Engineering hybrid genes without the use of restriction enzymes: gene splicing by overlap extension.
1989,
Pubmed
Lee,
Mechanism of calcium channel blockade by verapamil, D600, diltiazem and nitrendipine in single dialysed heart cells.
1983,
Pubmed
McDonald,
Cat ventricular muscle treated with D600: characteristics of calcium channel block and unblock.
1984,
Pubmed
Pragnell,
Calcium channel beta-subunit binds to a conserved motif in the I-II cytoplasmic linker of the alpha 1-subunit.
1994,
Pubmed
Stea,
Localization and functional properties of a rat brain alpha 1A calcium channel reflect similarities to neuronal Q- and P-type channels.
1994,
Pubmed
,
Xenbase
Striessnig,
Structural basis of drug binding to L Ca2+ channels.
1998,
Pubmed
Walker,
A beta 4 isoform-specific interaction site in the carboxyl-terminal region of the voltage-dependent Ca2+ channel alpha 1A subunit.
1998,
Pubmed
Zamponi,
Beta subunit coexpression and the alpha1 subunit domain I-II linker affect piperidine block of neuronal calcium channels.
1996,
Pubmed
,
Xenbase
Zühlke,
Ca2+ channel sensitivity towards the blocker isradipine is affected by alternative splicing of the human alpha1C subunit gene.
1998,
Pubmed
,
Xenbase
