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Calcium channel block by (-)devapamil is affected by the sequence environment and composition of the phenylalkylamine receptor site.
Degtiar VE
,
Aczél S
,
Döring F
,
Timin EN
,
Berjukow S
,
Kimball D
,
Mitterdorfer J
,
Hering S
.
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The pore-forming alpha 1 subunit of L-type calcium (Ca2+) channels is the molecular target of Ca2+ channel blockers such as phenylalkylamines (PAAs). Association and dissociation rates of (-)devapamil were compared for a highly PAA-sensitive L-type Ca2+ channel chimera (Lh) and various class A Ca2+ channel mutants. These mutants carry the high-affinity determinants of the PAA receptor site in a class A sequence environment. Apparent drug association and dissociation rate constants were significantly affected by the sequence environment (class A or L-type) of the PAA receptor site. Single point mutations affecting the high-affinity determinants in segments IVS6 of the PAA receptor site, introduced into a class A environment, reduced the apparent drug association rates. Mutation I1811M in transmembrane segment IVS6 (mutant AL25/-I) had the highest impact and decreased the apparent association rate for (-)devapamil by approximately 30-fold, suggesting that this pore-lining isoleucine in transmembrane segment IVS6 plays a key role in the formation of the PAA receptor site. In contrast, apparent drug dissociation rates of Ca2+ channels in the resting state were almost unaffected by point mutations of the PAA receptor site.
Bean,
Nitrendipine block of cardiac calcium channels: high-affinity binding to the inactivated state.
1984, Pubmed
Bean,
Nitrendipine block of cardiac calcium channels: high-affinity binding to the inactivated state.
1984,
Pubmed
Birnbaumer,
The naming of voltage-gated calcium channels.
1994,
Pubmed
Catterall,
Receptor sites for Ca2+ channel antagonists.
1992,
Pubmed
Catterall,
Structure and function of voltage-gated ion channels.
1995,
Pubmed
Diochot,
Dihydropyridines, phenylalkylamines and benzothiazepines block N-, P/Q- and R-type calcium currents.
1995,
Pubmed
Dunlap,
Exocytotic Ca2+ channels in mammalian central neurons.
1995,
Pubmed
Döring,
Transfer of L-type calcium channel IVS6 segment increases phenylalkylamine sensitivity of alpha1A.
1996,
Pubmed
,
Xenbase
Glossmann,
Molecular properties of calcium channels.
1990,
Pubmed
Grabner,
Calcium channels from Cyprinus carpio skeletal muscle.
1991,
Pubmed
Grabner,
Transfer of 1,4-dihydropyridine sensitivity from L-type to class A (BI) calcium channels.
1996,
Pubmed
Hering,
Mechanism of calcium channel block by D600 in single smooth muscle cells from rabbit ear artery.
1989,
Pubmed
Hering,
Modulation of calcium channels in arterial smooth muscle cells by dihydropyridine enantiomers.
1993,
Pubmed
Hering,
Transfer of high sensitivity for benzothiazepines from L-type to class A (BI) calcium channels.
1996,
Pubmed
,
Xenbase
Hescheler,
Does the organic calcium channel blocker D600 act from inside or outside on the cardiac cell membrane?
1982,
Pubmed
Hille,
Local anesthetics: hydrophilic and hydrophobic pathways for the drug-receptor reaction.
1977,
Pubmed
Hockerman,
Molecular determinants of high affinity phenylalkylamine block of L-type calcium channels.
1995,
Pubmed
Hofmann,
Molecular basis for Ca2+ channel diversity.
1994,
Pubmed
Horton,
Engineering hybrid genes without the use of restriction enzymes: gene splicing by overlap extension.
1989,
Pubmed
Ishibashi,
Block of P-type Ca2+ channels in freshly dissociated rat cerebellar Purkinje neurons by diltiazem and verapamil.
1995,
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
Mikami,
Primary structure and functional expression of the cardiac dihydropyridine-sensitive calcium channel.
1989,
Pubmed
,
Xenbase
Mori,
Primary structure and functional expression from complementary DNA of a brain calcium channel.
1991,
Pubmed
,
Xenbase
Nawrath,
Kinetics and state-dependent effects of verapamil on cardiac L-type calcium channels.
1997,
Pubmed
Qu,
Molecular determinants of drug access to the receptor site for antiarrhythmic drugs in the cardiac Na+ channel.
1995,
Pubmed
,
Xenbase
Sanger,
DNA sequencing with chain-terminating inhibitors.
1977,
Pubmed
Starmer,
Phasic ion channel blockade. A kinetic model and parameter estimation procedure.
1985,
Pubmed
Timin,
A method for estimation of drug affinity constants to the open conformational state of calcium channels.
1992,
Pubmed
