Omecamtiv Mecarbil Abolishes Length-Mediated Increase in Guinea Pig Cardiac Myofiber Ca(2+) Sensitivity.

Omecamtiv Mecarbil Abolishes Length-Mediated Increase in Guinea Pig Cardiac Myofiber Ca(2+) Sensitivity. Biophys J. 2017 Aug 22;113(4):880-888 Authors: Gollapudi SK, Reda SM, Chandra M Abstract Omecamtiv mecarbil (OM) is a pharmacological agent that augments cardiac contractile function by enhancing myofilament Ca(2+) sensitivity. Given that interventions that increase myofilament Ca(2+) sensitivity have the potential to alter length-dependent activation (LDA) of cardiac myofilaments, we tested the influence of OM on this fundamental property of the heart. This is significant not only because LDA is prominent in cardiac muscle but also because it contributes to the Frank-Starling law, a mechanism by which the heart increases stroke volume in response to an increase in venous return. We measured steady-state and dynamic contractile indices in detergent-skinned guinea pig (Cavia porcellus) cardiac muscle fibers in the absence and presence of 0.3 and 3.0 μM OM at two different sarcomere lengths (SLs), short SL (1.9 μm) and long SL (2.3 μm). Myofilament Ca(2+) sensitivity, as measured by pCa50 (-log of [Ca(2+)]free concentration required for half-maximal activation), increased significantly at both short and long SLs in OM-treated fibers when compared to untreated fibers; however, the magnitude of increase in pCa50 was twofold greater at short SL than at long SL. A consequence of this greater increase in pCa50 at short SL was that pC...
Source: Biophysical Journal - Category: Physics Authors: Tags: Biophys J Source Type: research