Stretch‐Induced Increase in Cardiac Contractility Is Independent of Myocyte Ca2+ While Block of Stretch Channels by Streptomycin Improves Contractility After Ischemic Stunning
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DOI: 10.14814/phy2.12486, PubMed Central: PMCID: PMC4562572
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 crossbridge 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.
Rhodes, Samhita S.; Camara, Amadou KS; Aldakkak, Mohammed; Heisner, James S.; and Stowe, David F., "Stretch‐Induced Increase in Cardiac Contractility Is Independent of Myocyte Ca2+ While Block of Stretch Channels by Streptomycin Improves Contractility After Ischemic Stunning" (2015). Biomedical Engineering Faculty Research and Publications. 422.
Accepted version. Physiological Reports, Vol 3, No. 8 (August 18, 2015): e12486. DOI. © 2015 Wiley and The Physiological Society. Used with permission.