Length Dependent Activation Develops Virtually Instantaneously (<5MS) in Guinea Pig Myocardium

Abstract

Myofilament length dependent activation (LDA) is a universal property of striated muscle. The molecular mechanisms that underlie LDA are poorly understood. Additionally, the rate at which LDA appears following a change in sarcomere length (SL) is unknown. Accordingly, we compared sub-maximal activation (pCa 5.7;∼60%Fo) at steady state SL to sub-maximal activation following a rapid stretch to the same SL. Isolated skinned guinea-pig myofibrils were attached to glass micro-tools positioned on the stage of an inverted microscope (15C); one probe functioned as a force cantilever, while the other probe was attached to a rapid displacement generator; a Ca2+ pulse was applied by rapid translation of a double-barreled perfusion pipette (de Tombe, AJP, 2007). Activations were performed at SL=2.3µm (steady state), or after a rapid (5ms) stretch from SL=2.0µm. Steady state active force (62+2.8%) was similar to rapid stretch force (61+2.7%, respectively). Activation kinetics, measured as the time it takes for force to reach 50% of steady state force (T50), were also similar between steady state and rapid stretch (0.88+0.03s and 0.86+0.4s, respectively). Our data suggests that the transduction of the “length signal” in guinea-pig cardiac myofibrils occurs within 5 ms.