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 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
Z
Z
Departments of Physiology and Medicine and University Health Network (General Division), University of Toronto, CCRW 3-802, Toronto, Ontario, Canada.
Myers
R
R
Kaprielian
R
R
Banijamali
H S
HS
Backx
P H
PH
D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002227:Carbazoles / Q000494:pharmacology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006352:Heart Ventricles; D066298:In Vitro Techniques; D026121:Indole Alkaloids; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D013997:Time Factors
D002227:Carbazoles; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; D047428:Protein Kinase Inhibitors; D011943:Receptors, Adrenergic, beta; C049985:staurosporine aglycone; D002118:Calcium