Sc. Calaghan et al., Cyclic AMP but not phosphorylation of phospholamban contributes to the slow inotropic response to stretch in ferret papillary muscle, PFLUG ARCH, 437(5), 1999, pp. 780-782
cAMP has been suggested to mediate the increased intracellular Ca2+ transie
nt and contraction seen during the slow response to stretch in cardiac musc
le. We measured cAMP in ferret papillary muscles stretched from 80-85% to 9
8% of their length at which maximum active tension is produced (L-max) for
15 min. cAMP was significantly (P<0.05) increased by 53% in muscles at the
longer length which showed the slow response compared with controls. By con
trast, in a population of muscles that were stretched but did not show the
slow response, cAMP was not significantly different from that in muscles at
the short length. Although cAMP can increase sarcoplasmic reticulum (SR) C
a2+ uptake by phosphorylation of phospholamban, we found no:significant eff
ect of stretch on phosphorylation of phospholamban at either Ser(16) or Thr
(17). Further support for the hypothesis that cAMP is a mediator of the slo
w response was obtained by exposure of some muscles to the cell-permeable c
AMP antagonist 8-bromo, adenosine 3',5'-cyclic monophosphorothioate, Rp iso
mer (Rp-8-Br-cAMPS, (2.5-10 mu M). The slow response was reduced by 30% (P<
0.05) in the presence of this antagonist. Our results not only provide evid
ence for the mediation of the slow response to stretch by cAMP, they also s
uggest that cAMP may rise in an intracellular compartment inaccessible to t
he SR.