APStracts 2:0041C, 1995.

Cyclic adp-ribose and related compounds activate the sheep skeletal sarcoplasmic reticulum ca2+-release channel. Sitsapesan, Rebecca, and Alan J. Williams. Dr. Rebecca Sitsapesan, Telephone: 071-352-8121 ext. 3321, Fax: 071-376- 3442

APStracts 2:0041C, 1995.

It has been suggested that cyclic ADP-ribose (cADPR) can activate only non -skeletal isoforms of the ryanodine-sensitive Ca2+-release channel (2,5,9,10). We now demonstrate that cADPR is an effective activator of sheep skeletal sarcoplasmic reticulum (SR) Ca2+-release channels incorporated into planar phospholipid bilayers in the presence of activating levels of cytosolic Ca2+. In addition, the precursor of cADPR, [beta]-nicotinamide adenine dinucleotide ([beta]NAD+) and the metabolite, ADP-ribose also increase the open probability (Po) of skeletal SR Ca2+-release channels in micromolar concentrations. At low concentrations of cADPR (1 _M), the mechanism for the increase in Po is an increase in the frequency of channel openings with no increase in the duration of the open events. We also show that the effect of cADPR is dependent on luminal [Ca2+]. cADPR has no effect on Po when the luminal [Ca2+] is <40 _M. However at millimolar concentrations of luminal Ca2+ cADPR (1 _M and 10 _M ) increases Po in the presence of activating cytosolic Ca2+.

Received 28 June 1994; accepted in final form 29 November 1994
APS Manuscript Number C0369-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1994 The American Physiological Society.
Published in APStracts on 27 February 1995.