Activation and Relaxation Kinetics in Isolated Guinea-Pig Myofibrils: Impact of Sarcomere Length

Abstract

Myofilament length dependent activation is a universal property of striated muscle that is most pronounced in myocardium. The mechanisms that underlie length dependency are incompletely understood. Accordingly, here we tested the hypothesis that sarcomere length (SL) affects the rate of force activation and/or force relaxation in response to a saturating pulse of Ca2+. Isolated skinned guinea-pig myofibrils were attached to glass micro-tools positioned on the stage of an inverted microscope (15 C); one probe functioned as a force probe cantilever, while the other probe was attached to a rapid displacement generator; the Ca2+ pulse was applied by rapid translation of a double-barreled perfusion pipette (de Tombe, AJP, 2007). Activations were performed at long (SL=2.06 ± 0.03 μm) and short (SL=1.85 ± 0.01; n=5) length. As expected, SL modulated maximum Ca2+ saturated force ∼20%. Both the rate of force redevelopment following a rapid release-restretch maneuver (kTr; ∼26%) and Ca2+ activated force development (kCa;∼14%) were faster at the long SL. In contrast, SL did not modulate any parameters of force relaxation following rapid removal of activator Ca2+. Our data suggest that length dependent myofilament activation in the heart may be the result of differential modulation of activation dynamics in response to changes in sarcomere length.