Activation dependence of isotonic transient in response to step tension reduction in cardiac muscle segment during barium contracture

Abstract

To clarify the activation-dependence of dynamic mechanical characteristics of contracting cardiac muscle, we analysed the healthy central segment length (SL) response to step decrease in tension at two different levels of barium contracture (0.2 mM and 0.5 mM Ba2+) in rat papillary muscles with a fixed initial SL. The time course of this response is thought to reflect the kinetics of actin-myosin interaction. The muscle was released stepwise from the steady contracture tension (Tc) to new steady tension levels (Tr) of varying magnitudes at 22 degrees C. The SL responses consisted of four phases at Tr/Tc greater than 0.3. The amplitude of shortening in the second phase, after the initial rapid and minute shortening in the first phase, increased with an increase in amplitude of step tension reduction, and was greater at the higher activation level when compared at an identical amount of Tr/Tc. The fourth phase, after the remarkable lengthening in the third phase, was an extremely slow and minute shortening toward a new steady SL under the new tension. The duration of the second and third phase was quite insensitive to activation level at Tr/Tc greater than 0.85, but became longer at the higher activation level with larger amounts of tension reduction. The velocity measured from the initial quasi-steady SL shortening in the second phase increased significantly with the increase in activation level. These results are discussed in terms of cross-bridge kinetics underlying the isotonic SL transients at two different activation levels.

P‐glycoprotein‐mediated transcellular transport of MDR‐reversing agents

“…We have reported that the immunosuppressive agents cyclosporin A and FK506 are transported by Pglycoprotein [15]. These results and the results shown here indicate that lipophilic MDR modulators are divided into two types: ones which are transported by P-glycoprotein, and the others which are not.…”