Rate-dependent changes in twitch force duration in rat cardiac trabeculae are likely due to intrinsic features of contractile or Ca2+-handling proteins rather than PKA or CaM/kinase II activity.
We examined the mechanisms for rate-dependent changes in twitch force duration by simultaneously measuring force and Ca2+i in rat cardiac trabeculae. 2. Peak force decreased when the rate of stimulation was increased from 0.2 to 0.5 Hz, whilst it increased from 1 to 2 Hz. Over the same range of frequencies, peak Ca2+i transients increased monotonically, whilst both force and Ca2+i transient duration were abbreviated. 3. Changes in peak force or peak Ca2+i transients were not responsible for the changes in force or Ca2+i transient duration. 4. The changes in twitch force and Ca2+i transient duration were completed roughly within one beat following an abrupt change in the rate of stimulation. 5. Rate-dependent changes resembled those observed with isoproterenol (isoprenaline) application. However, kinase inhibitors (i.e. K252-a, H-89, KN-62 and KN-93) had no effect on the rate-dependent changes of twitch force and Ca2+i transient kinetics, suggesting that protein kinase A (PKA), protein kinase PKG) and Ca2+-calmodulin-dependent protein kinase II (CaM/kinase II) were not responsible for these kinetic changes. 6. Despite the changes in twitch force and Ca2+i transient kinetics, the rate-limiting step for the rate-dependent force relaxation still resides at the level of the contractile proteins. 7. Our results suggest that rate-dependent changes in force and Ca2+i transients do not depend on PKA or CaM/kinase II activity but might result from intrinsic features of the contractile and/or Ca2+-handling proteins.
Kassiri et al. (Sat,) studied this question.
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