title: Force staircase kinetics in mammalian cardiac muscle: modulation by muscle length.
abstract: 1. Quiescent cat papillary muscles were stimulated to contract regularly at L(max), the length at which force production is optimal, and at 0.85 L(max). The resulting increase in force production (rate staircase) at each length was characterized as an exponential function.2. When stimulated from quiescence at 24 min(-1) in a bathing fluid [Ca(2+)] of 2.5 mM, sixteen of twenty-three muscles exhibited biexponential increases in force production at both lengths. The coefficients of the exponential function at L(max) were 1.5-2 times greater than their counterparts at the shorter length, and this length difference was highly significant. When the force staircases were normalized to the peak developed force attained at each length, the number of beats to attain 25, 50, 75, and 98% of peak force at 0.85 L(max) was approximately twice that required at L(max).3. At a given length the force staircase (1) exhibited a dependency on the number of beats rather than on stimulation frequency over a range of 12-60 min(-1), (2) was accelerated by increasing the bathing fluid [Ca(2+)] from 1.0 to 5.0 mM, (3) was accelerated in the presence of isoproterenol, and (4) was retarded in the presence of DL-verapamil. Over the entire range of bathing fluid [Ca(2+)] and at all stimulation frequencies 24 min(-1) and above, more beats were required to complete a given level of the normalized staircase at 0.85 L(max) than at L(max). There was no length difference in the presence of verapamil. These data suggest that transsarcolemmal Ca(2+) influx is an important determinant of the kinetics of the force staircase, and the length dependence of the latter indicates that muscle length is an important determinant of transsarcolemmal Ca(2+) influx.4. This conclusion was strengthened by the results of additional studies in which the [Ca(2+)] of the bathing fluid was abruptly increased from 1.0 to 5.0 mM with the muscle beating in the steady state. The resulting increase in force production (Ca(2+) staircase) was described by a monoexponential function with a greater coefficient at L(max) than 0.85 L(max); when normalized to the peak force difference in the two [Ca(2+)] at each length, a given level of the staircase was achieved in significantly fewer beats at L(max) than at the shorter length.5. The data provide a mechanism which, in part, explains the length dependence of excitation-contraction coupling in cardiac muscle with intact sarcolemmae.
mesh_terms: D000818:Animals; D001699:Biometry; D002118:Calcium / Q000494:pharmacology; D002415:Cats; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000187:drug effects / Q000502:physiology*; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology; D014700:Verapamil / Q000494:pharmacology
chemical_list: D014700:Verapamil; D007545:Isoproterenol; D002118:Calcium