Z. Kassiri et al., Rate-dependent changes of twitch force duration in rat cardiac trabeculae:a property of the contractile system, J PHYSL LON, 524(1), 2000, pp. 221-231
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.