The physical association of regulatory enzymes and ion channels at relevant intracellular sites contributes to the diversity and specificity of second messenger-mediated signal transduction in cells. mAKAP is a scaffolding protein that targets the cAMP-dependent protein kinase A and phosphodiesterase type 4D3 to the nuclear envelope of differentiated cardiac myocytes. Here we present data that ...

The anthraquinones, doxorubicin, mitoxantrone, daunorubicin and rubidazone are shown to be potent stimulators of Ca2+ release from skeletal muscle sarcoplasmic reticulum (SR) vesicles and to trigger transient contractions in chemically skinned psoas muscle fibers. These effects of anthraquinones are the direct consequence of their specific interaction with the [3H] ryanodine receptor complex, w...

Calcium is a universal second messenger. The temporal and spatial information that is encoded in Ca(2+)-transients drives processes as diverse as neurotransmitter secretion, axonal outgrowth, immune responses and muscle contraction. Ca(2+)-release from intracellular Ca(2+) stores can be triggered by diffusible second messengers like Ins P (3), cyclic ADP-ribose or nicotinic acid-adenine dinucle...

We examined whether Ca(2+) induced Ca(2+) release through ryanodine receptors is involved in the conditioning of specific morphologic changes at the axon terminals of type B photoreceptors in the isolated circumesophageal ganglion of Hermissenda. Calcium chelation by bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid prevented the conformational change at the terminals after five paired pres...

signal activates specialized Ca 2 1 release channels, the ryanodine receptors (RyRs), in the sarcoplasmic reticulum (SR). This process is called Ca 2 1 -induced Ca 2 1 release (CICR). Intuitively, the CICR process should be self-regenerating because the Ca 2 1 released from the SR should feedback and activate further SR Ca 2 1 release. However, the CICR process is precisely controlled in the he...

Tryptic digestion of the junctional sarcoplasmic reticulum membranes in sucrose but not NaCl buffer leads to complete loss of ryanodine binding capacity. The presence of MgCl2 in the sucrose buffer prevents the loss of ryanodine binding by the trypsin treatment. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the treated membranes reveal that the 400-kDa protein band disappeared un...

Calcium current in mammalian ventricular muscle is altered in the presence of ryanodine. Previous studies performed on rat ventricular cells have shown a slowing of Ca2+ current inactivation and suggest the hypothesis that ryanodine, by reducing the release of Ca2+ from the sarcoplasmic reticulum, reduces the availability of Ca2+ for inactivation of Ca2+ current (Ca(2+)-dependent inactivation)....

Short title: Ryanodine receptors, voltage-gated calcium channels and PKA Abstract We present the review of the data from the literature about relationship between ryanodine receptors and voltage-gated calcium channels in myocardium, and also how both of them are related to protein kinase A. Ryanodine receptors, which have three subtypes (RyR1-3), are located on the membrane of sarcoplasmic reti...

The skeletal muscle relaxant dantrolene inhibits the release of Ca2+ from the sarcoplasmic reticulum during excitation-contraction coupling and suppresses the uncontrolled Ca2+ release that underlies the skeletal muscle pharmacogenetic disorder malignant hyperthermia; however, the molecular mechanism by which dantrolene selectively affects skeletal muscle Ca2+ regulation remains to be defined. ...

The Presenilins (PS) gene family is composed of two members: PS1 and PS2. Mutations in PSs are linked to familial Alzheimer’s disease (FAD) (1). PSs are the catalytic subunits of the γ-secretase multimolecular complex, which mediates the intramembranous cleavage of many type I membrane proteins, including amyloid precursor protein (APP) and Notch (2, 3). Cleavage of substrates produces secreted...