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The effects of KB-R7943, an inhibitor of reverse Na+/Ca2+ exchange,on the force of contraction of papillary muscles in the heart of the ground squirrel Spermophilus undulatus
Authors:A.?S.?Averin  author-information"  >  author-information__contact u-icon-before"  >  mailto:averin.icb@gmail.com"   title="  averin.icb@gmail.com"   itemprop="  email"   data-track="  click"   data-track-action="  Email author"   data-track-label="  "  >Email author,L.?S.?Kosarsky,S.?V.?Tarlachkov,V.?A.?Vekhnik,I.?V.?Averina,A.?E.?Alekseev,E.?E.?Fesenko,O.?V.?Nakipova
Affiliation:1.Institute of Cell Biophysics,Russian Academy of Sciences,Pushchino, Moscow oblast,Russia;2.Institute of the Biochemistry and Physiology of Microorganisms,Russian Academy of Sciences,Pushchino, Moscow oblast,Russia;3.Shemyakin Ovchinnikov Institute of Bioorganic Chemistry (Pushchino Branch),Russian Academy of Sciences,Pushchino, Moscow oblast,Russia;4.Sprygin Zhiguli State Natural Reserve,Bakhilova Polyana,Zhigulyovsk, Samara Region,Russia;5.Institute of Theoretical and Experimental Biophysics,Russian Academy of Sciences,Pushchino, Moscow oblast,Russia;6.Department of Molecular Pharmacology and Experimental Therapeutics,Rochester,USA
Abstract:We investigated the effect of KB-R7943, an inhibitor of the reverse mode of Na+/Ca2+ exchanger, on the force of isometric contractions, the contractile force–frequency relationship and post-rest potentiation (a qualitative parameter of Ca2+ levels in sarcoplasmic reticulum) in the right ventricle papillary muscles isolated from ground squirrel hearts during summer (June, n = 4) and autumn (October, n = 4) activities. In the presence of 1.8 mM Ca2+at 36°C, 1–1.5 hours-long treatment of the summer papillary muscles with KB-R7943 produced no significant effects on the contractile indices at the majority of stimulation frequencies. In the autumn papillary muscles KB-R7943 induced a 40–50% decrease in the force of contraction (negative inotropic effect) at low stimulation frequencies (0.1–0.3 Hz) without any significant effect at higher stimulation frequencies (0.4–3.0 Hz). Furthermore, in this group, KB-R7943 suppressed the post-rest potentiation of contractility by 50 ± 21% at pause durations exceeding 120 s. These observations indicate that KB-R7943 can affect Ca2+ levels in sarcoplasmic reticulum and that Na+/Ca2+ exchange may contribute to the physiological remodeling of intracellular Ca2+ homeostasis in myocardium of hibernating animals prior their transition to a hypometabolic torpid state.
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