Magnitude of length-dependent changes in contractile properties varies with titin isoform in rat ventricles

Patel JR, Pleitner JM, Moss RL, Greaser ML. Magnitude of length-dependent changes in contractile properties varies with titin isoform in rat ventricles. Am J Physiol Heart Circ Physiol 302: H697-H708, 2012. First published December 2, 2011; doi:10.1152/ajpheart.00800.2011.-The effects of differential expression of titin isoforms on sarcomere length (SL)-dependent changes in passive force, maximum Ca2+-activated force, apparent cooperativity in activation of force (n(H)), Ca2+ sensitivity of force (pCa(50)), and rate of force redevelopment (k(tr)) were investigated in rat cardiac muscle. Skinned right ventricular trabeculae were isolated from wild-type (WT) and mutant homozygote (Ho) hearts expressing predominantly a smaller N2B isoform (2,970 kDa) and a giant N2BA-G isoform (3,830 kDa), respectively. Stretching WT and Ho trabeculae from SL 2.0 to 2.35 mu m increased passive force, maximum Ca2+-activated force, and pCa(50), and it decreased nH and ktr. Compared with WT trabeculae, the magnitude of SL-dependent changes in passive force, maximum Ca2+-activated force, pCa(50), and n(H) was significantly smaller in Ho trabeculae. These results suggests that, at least in rat ventricle, the magnitude of SL-dependent changes in passive force, maximum Ca2+-activated force, pCa(50), n(H), and k(tr) is defined by the titin isoform.