Regulation of KCa-channel activity by cyclic ADP-ribose and ADP-ribose in coronary arterial smooth muscle. Am J Physiol 1998 Sep;275(3):H1002-10
Date
09/02/1998Pubmed ID
9724306DOI
10.1152/ajpheart.1998.275.3.H1002Scopus ID
2-s2.0-0031689064 (requires institutional sign-in at Scopus site) 17 CitationsAbstract
The enzymatic pathway responsible for the production and metabolism of cyclic ADP-ribose (cADP-R) in small bovine coronary arteries was characterized, and the role of cADP-R and ADP-ribose (ADP-R) in the regulation of the activity of large-conductance Ca2+-activated K+ (KCa) channels was determined in vascular smooth muscle cells (SMC) prepared from these vessels. We found that cADP-R and ADP-R were produced when the coronary arterial homogenates were incubated with 1 mM beta-NAD. The time course of the enzyme reactions showed that the maximal conversion rate (1.37 +/- 0.03 nmol . min-1 . mg protein-1) of beta-NAD to cADP-R was reached after 3 min of incubation. As incubation time was prolonged, the production of ADP-R was increased to a maximal rate of 3.66 +/- 0.03 nmol . min-1 . mg protein-1, whereas cADP-R production decreased. Incubation of the homogenate with cADP-R produced a time-dependent increase in the synthesis of ADP-R. Comparison of coronary arterial microsomes with cytosols shows that the production of both cADP-R and ADP-R in microsomes was significantly greater. In excised inside-out membrane patches of single coronary SMC, the KCa channels were activated when beta-NAD, the precursor for both cADP-R and ADP-R, was applied to the internal surface. This effect of beta-NAD may be associated with the production of ADP-R, because the KCa-channel activity was increased by ADP-R in a concentration-dependent manner. The open-state probability of the KCa channels increased from a control level of 0.08 +/- 0.03 to 0.17 +/- 0.05 even at the lowest ADP-R concentration (0.1 microM) studied. However, cADP-R reduced the KCa-channel activity, and the threshold concentration of cADP-R that decreased the average channel activity of the KCa channels was 1 microM. These results provide evidence that cADP-R is produced and metabolized in the coronary arterial smooth muscle and that a cADP-R/ADP-R pathway participates in the control of the KCa-channel activity in vascular SMC.
Author List
Li PL, Zou AP, Campbell WBAuthor
William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
ADP-ribosyl CyclaseAdenosine Diphosphate Ribose
Animals
Calcium
Cattle
Chromatography, High Pressure Liquid
Coronary Vessels
Cyclic ADP-Ribose
Cytosol
Electric Conductivity
Kinetics
Membrane Potentials
Microsomes
Muscle, Smooth, Vascular
NAD
NAD+ Nucleosidase
Phosphorus-Oxygen Lyases
Potassium Channels
