Stretch‐induced increase in cardiac contractility is independent of myocyte Ca2+ while block of stretch channels by streptomycin improves contractility after ischemic stunning

• Published in: Physiological reports 2015-08, Vol.3 (8), p.n/a
• Main Authors: Rhodes, Samhita S., Camara, Amadou K. S., Aldakkak, Mohammed, Heisner, James S., Stowe, David F.
• Format: Article
• Language: English
• Subjects: Contractility; cross‐bridges; heart; mathematical modeling; myoplasmic calcium; Original Research; stretch channels
• ISSN: 2051-817X; 2051-817X
• DOI: 10.14814/phy2.12486

Stretching the cardiac left ventricle (LV) enhances contractility but its effect on myoplasmic [Ca2+] is controversial. We measured LV pressure (LVP) and [Ca2+] as a function of intra‐LV stretch in guinea pig intact hearts before and after 15 min global stunning ± perfusion with streptomycin (STM), a stretch‐activated channel blocker. LV wall [Ca2+] was measured by indo‐1 fluorescence and LVP by a saline‐filled latex balloon inflated in 50 μL steps to stretch the LV. We implemented a mathematical model to interpret cross‐bridge dynamics and myofilament Ca2+ responsiveness from the instantaneous relationship between [Ca2+] and LVP ± stretching. We found that: (1) stretch enhanced LVP but not [Ca2+] before and after stunning in either control (CON) and STM groups, (2) after stunning [Ca2+] increased in both groups although higher in STM versus CON (56% vs. 39%), (3) STM‐enhanced LVP after stunning compared to CON (98% vs. 76% of prestunning values), and (4) stretch‐induced effects on LVP were independent of [Ca2+] before or after stunning in both groups. Mathematical modeling suggested: (1) cooperativity in cross‐bridge kinetics and myofilament Ca2+ handling is reduced after stunning in the unstretched heart, (2) stunning results in depressed myofilament Ca2+ sensitivity in the presence of attached cross‐bridges regardless of stretch, and (3) the initial mechanism responsible for increased contractility during stretch may be enhanced formation of cross‐bridges. Thus stretch‐induced enhancement of contractility is not due to increased [Ca2+], whereas enhanced contractility after stunning in STM versus CON hearts results from improved Ca2+ handling and/or enhanced actinomyosin cross‐bridge cycling. We implemented a mathematical model to interpret cross‐bridge dynamics and myofilament Ca2+ responsiveness from the instantaneous relationship between [Ca2+] and LVP ± stretching. We found that: (1) stretch enhanced LVP but not [Ca2+] before and after stunning whereas stunning increased [Ca2+]. Modeling suggested that the initial mechanism responsible for increased contractility during stretch may be enhanced formation of cross‐bridges rather than increased sensitivity to [Ca2+].