AJP - Regulatory, Integrative and Comparative Physiology, Vol 248, Issue 1 54-R62, Copyright © 1985 by American Physiological Society
Contribution of activation-inactivation dynamics to the impairment of relaxation in hypoxic cat papillary muscle
A. Pasipoularides, I. Palacios, W. Frist, S. Rosenthal, J. B. Newell and W. J. Powell Jr
Previous investigation of conventional isometric twitches of normothermic
cat papillary muscle has shown that hypoxia prolongs relaxation, and this
prolongation is actually accentuated during early reoxygenation. Our aim
was to identify how hypoxia and reoxygenation affect the coupled processes
of activation and inactivation that govern the time course of internally
generated contractile tension (Ti). Activation and inactivation are modeled
as first-order processes with rate constants ka and ki, respectively, and
the overall isometric muscle as an underdamped second-order lag system
driven by Ti. The analytical expression (To) for the externally recorded
tension is dominated by two exponential terms incorporating ka and ki.
Accurate least-squares fits of digitized twitches to To yielded estimates
of ka and ki at 1- to 3-min intervals during control oxygenation, hypoxia,
and early and late reoxygenation. Results follow. Compared with control,
normothermic hypoxia prolonged activation [at 15 min ka decreased 61% from
control, 35.5 +/- 6 (SE) s-1, P less than 0.05] and accelerated
inactivation (at 15 min, ki increased 69% from control, 6.0 +/- 0.5 s-1, P
less than 0.05). In early reoxygenation (1-3 min) activation remained
impaired and inactivation returned to control levels (ki decreased 16% from
control, NS). In late reoxygenation (15 min) both processes reverted to
control. Thus inactivation kinetics can be dissociated from activation
kinetics. Impaired relaxation in normothermic hypoxia is due to prolonged
activation, whereas inactivation is actually accelerated. The further
impairment of relaxation in early reoxygenation is due to rapid return of
inactivation to control at a time when activation is still prolonged.
