Lack of effect of cADP-ribose and NAADP on the activity of skeletal muscle and heart ryanodine receptors.

The calcium release channels/ryanodine receptors (RyRs) are potential/putative targets of cADPR (cyclic ADP-ribose) action in many tissue systems. In striated muscles, where RyRs predominate, cADPR action on these channels is controversial. Here cADPR modulation of cardiac and skeletal muscle RyR channels was tested. We considered factors reported as necessary for cADPR action, such as the presence of calmodulin and/or FK binding proteins (FKBPs). We found: 1) The RyR channel isoforms were insensitive to cADPR (or its metabolite NAADP [nicotinic acid adenine dinucleotide phosphate]) under all conditions examined, as studied by: 1a) single channel recordings in planar lipid bilayers; 1b) macroscopic behavior of the RyRs in sarcoplasmic reticulum (SR) microsomes (including crude microsome preparations likely to retain putative cADPR cofactors) at room temperature and at 37 degrees C (net energized Ca2+ uptake or passive Ca2+ leak); 2) [32P]cADPR did not bind significantly to SR microsomes; 3) cADPR did not affect FKBP association to SR membranes. We conclude that cADPR does not interact directly with RyRs or RyR-associated SR proteins. Our results under in vitro conditions suggest that c ADPR effects on Ca2+ signaling observed in vivo in mammalian striated muscle cells may reflect indirect modulation of RyRs or RyR-independent Ca2+ release systems.

Copello JA ，Qi Y ，Jeyakumar LH ，Ogunbunmi E ，Fleischer S ... -  《CELL CALCIUM》

Nicotinic acid-adenine dinucleotide phosphate activates the skeletal muscle ryanodine receptor.

Hohenegger M ，Suko J ，Gscheidlinger R ，Drobny H ，Zidar A ... -  《-》

Cyclic ADP-ribose increases Ca2+ removal in smooth muscle.

Bradley KN ，Currie S ，MacMillan D ，Muir TC ，McCarron JG ... -  《JOURNAL OF CELL SCIENCE》

cADP-ribose activates reconstituted ryanodine receptors from coronary arterial smooth muscle.

Li PL ，Tang WX ，Valdivia HH ，Zou AP ，Campbell WB ... -  《AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY》

Novel mechanisms involved in superoxide anion radical-triggered Ca2+ release from cardiac sarcoplasmic reticulum linked to cyclic ADP-ribose stimulation.

Kumasaka S ，Shoji H ，Okabe E 《ANTIOXIDANTS & REDOX SIGNALING》