Journal
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Volume 280, Issue 1, Pages H208-H215Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.2001.280.1.H208
Keywords
adenosine 3 ',5 '-cyclic diphosphate-ribose; calcium mobilization; vascular smooth muscle; coronary artery
Funding
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL051055, R01HL057244, R29HL057244] Funding Source: NIH RePORTER
- NHLBI NIH HHS [HL-57244, HL-51055] Funding Source: Medline
Ask authors/readers for more resources
The present study was designed to test the hypothesis that cADP-ribose (cADPR) increases Ca2+ 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 Ca2+ 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 (NPo) of the channels in the presence of ryanodine (0.01-1 muM) and imperatoxin A (100 nM). A high concentration of ryanodine (50 muM) and ruthenium red (40-80 muM) substantially inhibited the activity of RYR/Ca2+ release channels. Caffeine (0.5-5 mM) markedly increased the NPo of these Ca2+ release channels of the SR, but D-myoinositol 1,4,5-trisphospate and heparin were without effect. Cyclic ADPR significantly increased the NPo of these Ca2+ release channels of SR in a concentration-dependent manner. Addition of cADPR (0.01 muM) into the cis bath solution produced a 2.9-fold increase in the NPo of these RYR/Ca2+ release channels. An eightfold increase in the NPo of the RYR/Ca2+ release channels (0.0056 +/- 0.001 vs. 0.048 +/- 0.017) was observed at a concentration of cADPR of 1 muM. The effect of cADPR was completely abolished by ryanodine (50 muM). In the presence of cADPR, Ca2+-induced activation of these channels was markedly enhanced. These results provide evidence that cADPR activates RYR/Ca2+ release channels on the SR of CASMCs. It is concluded that cADPR stimulates Ca2+ release through the activation of RYRs on the SR of these smooth mucle cells.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available