Faculty Collaboration Database

cADP-ribose activates reconstituted ryanodine receptors from coronary arterial smooth muscle. Am J Physiol Heart Circ Physiol 2001 Jan;280(1):H208-15

Date

12/21/2000

Pubmed ID

11123235

DOI

10.1152/ajpheart.2001.280.1.H208

Scopus ID

2-s2.0-0035019512 (requires institutional sign-in at Scopus site)   75 Citations

Abstract

The present study was designed to test the hypothesis that cADP-ribose (cADPR) increases Ca(2+) release through activation of ryanodine receptors (RYR) on the sarcoplasmic reticulum (SR) in coronary arterial smooth muscle cells (CASMCs). We reconstituted RYR from the SR of CASMCs into planar lipid bilayers and examined the effect of cADPR on the activity of these Ca(2+) release channels. In a symmetrical cesium methanesulfonate configuration, a 245 pS Cs(+) current was recorded. This current was characterized by the formation of a subconductance and increase in the open probability (NP(o)) of the channels in the presence of ryanodine (0.01-1 microM) and imperatoxin A (100 nM). A high concentration of ryanodine (50 microM) and ruthenium red (40-80 microM) substantially inhibited the activity of RYR/Ca(2+) release channels. Caffeine (0.5-5 mM) markedly increased the NP(o) of these Ca(2+) release channels of the SR, but D-myo-inositol 1,4,5-trisphospate and heparin were without effect. Cyclic ADPR significantly increased the NP(o) of these Ca(2+) release channels of SR in a concentration-dependent manner. Addition of cADPR (0.01 microM) into the cis bath solution produced a 2.9-fold increase in the NP(o) of these RYR/Ca(2+) release channels. An eightfold increase in the NP(o) of the RYR/Ca(2+) release channels (0.0056 +/- 0.001 vs. 0.048 +/- 0.017) was observed at a concentration of cADPR of 1 microM. The effect of cADPR was completely abolished by ryanodine (50 microM). In the presence of cADPR, Ca(2+)-induced activation of these channels was markedly enhanced. These results provide evidence that cADPR activates RYR/Ca(2+) release channels on the SR of CASMCs. It is concluded that cADPR stimulates Ca(2+) release through the activation of RYRs on the SR of these smooth mucle cells.

Author List

Li PL, Tang WX, Valdivia HH, Zou AP, Campbell WB

Author

William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenosine Diphosphate Ribose
Animals
Calcium
Calcium Channels
Cattle
Coronary Vessels
Cyclic ADP-Ribose
In Vitro Techniques
Lipid Bilayers
Membranes
Microsomes
Muscle, Smooth, Vascular
Ruthenium Red
Ryanodine Receptor Calcium Release Channel
Sarcoplasmic Reticulum
Ultrasonography