Rate-dependent changes of twitch force duration in rat cardiac trabeculae:a property of the contractile system

1. We examined the mechanisms for rate-dependent changes in twitch force du ration by simultaneously measuring force and [Ca2+](i) in rat cardiac trabe culae. 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 freq uencies, peak [Ca2+], 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 comple ted roughly within one beat following an abrupt change in the rate of stimu lation. 5. Rate-dependent changes resembled those observed with isoproterenol (isop renaline) application. However, kinase inhibitors (i.e. K252-a, K-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), prot ein kinase G (PKG) and Ca2+-calmodulin-dependent protein kinase II (CaM/kin ase II) were not responsible for these kinetic changes. 6. Despite the changes in twitch force and [Ca2+](i) transient kinetics, th e 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) t ransients do not depend on PKA or CaM/kinase II activity but might result f rom intrinsic features of the contractile and/or Ca2+-handling proteins.