AJP - Heart and Circulatory Physiology, Vol 256, Issue 4 1100-H1109, Copyright © 1989 by American Physiological Society
Slowly relaxing caffeine responses in rat ventricle: relationships of ryanodine and caffeine actions
D. W. Hilgemann, K. P. Roos and A. J. Brady
Department of Physiology, University of Texas Southwestern Medical Center, Dallas 75235-9040.
Contractile responses to 20 mM caffeine were compared in arterially
perfused rat right ventricle as tension, in intact rat myocytes as
shortening, and in Triton X-100-"skinned" rat myocytes as shortening and
stiffness. Responses in intact quiescent ventricle and membrane-disrupted
myocytes at -log molar Ca concentration (pCa) of 7.0-6.8 were similar;
force and stiffness rose quickly on application of caffeine and declined
incompletely toward base line over 20 min. Subsequent caffeine responses
were blunted. By contrast, in freshly isolated rat myocytes, rapid caffeine
exposures induced large phasic contractures, which relaxed for the most
part in 2-5 s. These responses were largely suppressed by 0.2 microM
ryanodine pretreatment at 35 degrees C but not by high ryanodine
concentrations (10 microM). Ryanodine was without effect on slowly relaxing
contractile responses in both intact ventricle and Triton X-100-treated
myocytes. The results are discussed in relation to the predicted effects of
a calcium store leak in a simple model of cardiac excitation-contraction
coupling. The results suggest that slowly relaxing caffeine contractures
can be caused entirely by direct actions of caffeine on myofilaments.
