Muscular dysgenesis (mdg) is a lethal autosomal, recessive mutation of mice. Skeletal muscle from dysgenic mice is paralyzed due to the failure of excitation-contraction (E-C) coupling. Considerable evidence indicates that this failure results from the absence of a specific gene product, the alpha 1 subunit of the skeletal muscle receptor for dihydropyridine calcium channel modifiers. This dihy...

Antibodies against the subunits of the dihydropyridine-sensitive L-type calcium channel of skeletal muscle were tested for their ability to immunoprecipitate the high affinity (ICd = 0.13 nM) "'I-w-conotoxin GVIA receptor from rabbit brain membranes. Monoclonal antibody VD21 against the B subunit of the dihydropyridine receptor from skeletal muscle specifically immunoprecipitated up to 86% of t...

Ten synthetic dihydropyridine analogues were investigated for their ability to reverse drug resistance in a multidrug-resistant human carcinoma cell line, KB-Cl. Four dihydropyridine analogues completely reversed the resistance, three lowered the resistance, and three had little effect. The radioactive photoactive dihydropyridine calcium channel blocker, [3H]azidopine, photolabels P-glycoprotei...

cancer is a leading cause of death worldwide. despite the availability of several chemotherapeutic drugs, there is still a great need for more efficient agents for a better management of cancer. in this contribution, a series of 11 dhps (4a, 4b & 7a-i) were synthesized and evaluated for their cytotoxic effect against mcf-7, ls180, and molt-4 cancer cell lines using mtt assay. synthesized 2,6-di...

The deficiency of dystrophin, a critical membrane stabilizing protein, in the mdx mouse causes an elevation in intracellular calcium in myocytes. One mechanism that could elicit increases in intracellular calcium is enhanced influx via the L-type calcium channels. This study investigated the effects of the dihydropyridines BAY K 8644 and nifedipine and alterations in dihydropyridine receptors i...

Voltage-dependent calcium channels play a role in many cellular phenomena. Very little is known about Ca2+ channels in Drosophila, especially those in muscles. Existing literature on neuronal Ca2+ channels of Drosophila suggests that their pharmacology may be distinct from that of vertebrate Ca2+ channels. This raises questions on the pharmacology and diversity of Ca2+ channels in Drosophila mu...

The influx of Ca ions into the presynaptic nerve terminal through ion channels is a key link between the action potential and the release of chemical transmitters. It is not clear, however, which types of Ca channel are involved in neurosecretion at vertebrate synapses. In particular, there is disagreement as to whether these channels are sensitive to dihydropyridine blockers, characteristic of...

Skeletal and cardiac dihydropyridine receptors function both as voltage-dependent L-type calcium channels (L-channels) and as critical proteins that trigger calcium release from the sarcoplasmic reticulum in muscle. In spite of these similarities, skeletal L-channels exhibit a markedly slower activation rate than cardiac L-channels. We investigated the mechanisms underlying this difference by c...

We investigated the mechanism of interaction of individual L-type channel amino acid residues with dihydropyridines within a dihydropyridine-sensitive a1A subunit (a1ADHP). Mutation of individual residues in repeat III and expression in Xenopus oocytes revealed that Thr is not required for dihydropyridine interaction but that bulky side chains (tyrosine, phenylalanine) in this position sterical...