Impact of titin strain on the cardiac slow force response Journal Article

Authors: Ait Mou, Y; Zhang, M; Martin, J. L.; Greaser, M. L.; de Tombe, P. P.
Article Title: Impact of titin strain on the cardiac slow force response
Abstract: Stretch of myocardium, such as occurs upon increased filling of the cardiac chamber, induces two distinct responses: an immediate increase in twitch force followed by a slower increase in twitch force that develops over the course of several minutes. The immediate response is due, in part, to modulation of myofilament Ca2+ sensitivity by sarcomere length (SL). The slowly developing force response, termed the Slow Force Response (SFR), is caused by a slowly developing increase in intracellular Ca2+ upon sustained stretch. A blunted immediate force response was recently reported for myocardium isolated from homozygous giant titin mutant rats (HM) compared to muscle from wild-type littermates (WT). Here, we examined the impact of titin isoform on the SFR. Right ventricular trabeculae were isolated and mounted in an experimental chamber. SL was measured by laser diffraction. The SFR was recorded in response to a 0.2 mum SL stretch in the presence of [Ca2+]o = 0.4 mM, a bathing concentration reflecting approximately 50% of maximum twitch force development at 25 degrees C. Presence of the giant titin isoform (HM) was associated with a significant reduction in diastolic passive force upon stretch, and approximately 50% reduction of the magnitude of the SFR; the rate of SFR development was unaffected. The sustained SL stretch was identical in both muscle groups. Therefore, our data suggest that cytoskeletal strain may underlie directly the cellular mechanisms that lead to the increased intracellular [Ca2+]i that causes the SFR, possibly by involving cardiac myocyte integrin signaling pathways.
Journal Title: Progress in biophysics and molecular biology
ISSN: 1873-1732; 0079-6107
Publisher: Elsevier Inc  
Journal Place: England
Date Published: 2017
Language: eng
Notes: LR: 20170708; CI: Copyright (c) 2017; GR: P01 HL062426/HL/NHLBI NIH HHS/United States; GR: R01 HL075494/HL/NHLBI NIH HHS/United States; GR: R01 HL077196/HL/NHLBI NIH HHS/United States; JID: 0401233; OTO: NOTNLM; 2017/02/20 [received]; 2017/06/17 [revised]; 2017/06/19 [accepted]; aheadofprint