Length-Dependent Activation of Contractility and Ca-Transient Kinetics in Auxotonically Contracting Isolated Rat Ventricular Cardiomyocytes

Autor: Oleg Lookin, Yuri Protsenko
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Inotrope
Contraction (grammar)
CELL ISOLATION
Physiology
isolated cardiomyocyte
030204 cardiovascular system & hematology
lcsh:Physiology
HEART VENTRICLE ENDDIASTOLIC PRESSURE
0302 clinical medicine
SARCOPLASMIC RETICULUM
HEART MUSCLE CONTRACTILITY
Myocyte
CELL KINETICS
Original Research
LENGTH DEPENDENT ACTIVATION
Frank–Starling law of the heart
lcsh:QP1-981
Ca-transient
AUXOTONIC CONTRACTION
rat myocardium
ISOLATED CARDIOMYOCYTE
HEART FUNCTION
STARLING LAW
FEMALE
medicine.medical_specialty
Diastole
chemistry.chemical_element
Calcium
FRANK-STARLING MECHANISM
ROOM TEMPERATURE
LENGTH-DEPENDENT ACTIVATION
Contractility
03 medical and health sciences
CARDIAC MUSCLE CELL
Internal medicine
Physiology (medical)
medicine
NONHUMAN
ARTICLE
Calcium metabolism
RAT MYOCARDIUM
MALE
CA-TRANSIENT
SARCOMERE LENGTH
length-dependent activation
CONTROLLED STUDY
030104 developmental biology
Endocrinology
chemistry
ANIMAL CELL
THAPSIGARGIN
auxotonic contraction
RAT
Frank-Starling mechanism
CALCIUM ION
Zdroj: Frontiers in Physiology
Frontiers in Physiology, Vol 10 (2019)
Popis: Length-dependent activation (LDA) of contraction is an important mechanism of proper myocardial function that is often blunted in diseases accompanied by deficient contractility and impaired calcium homeostasis. We evaluated how the extent of LDA is related to the decreased force in healthy rat myocardium under negative inotropic conditions that affect the calcium cycle. The length-dependent effects on auxotonic twitch and Ca-transient were compared in isolated rat ventricular cardiomyocytes at room temperature (“25C”) and near-physiological temperature (“35C”) in normal Tyrode and at 25°C with thapsigargin-depleted sarcoplasmic reticulum (“25C + Thap”). At the slack length, a similar negative inotropy in “35C” and “25C + Thap” was accompanied by totally different changes in Ca-transient amplitude, time-to-peak, and time-to-decline from peak to 50% amplitude. End-systolic/end-diastolic tension-sarcomere length relationships were obtained for each individual cell, and the ratio of their slopes, the dimensionless Frank-Starling Gain index, was 2.32 ± 0.16, 1.78 ± 0.09, and 1.37 ± 0.06 in “25C,” “35C” and “25C + Thap,” respectively (mean ± S.E.M.). Ca-transient diastolic level and amplitude did not differ between “25C” and “35C” at any SL, but in “35C” it developed and declined significantly faster. In contrast, thapsigargin-induced depletion of SERCA2a significantly attenuated and retarded Ca-transient. The relative amount of Ca2+ utilized by troponin C, evaluated by the integral magnitude of a short-lived component of Ca-transient decline (“bump”), increased by ~25% per each 0.05 μm increase in SL in all groups. The kinetics of the Ca-TnC dissociation, evaluated by the bump time-to-peak, was significantly faster in “35C” and slower in “25C + Thap” vs. “25C” (respectively, 63.7 ± 5.3 and 253.6 ± 8.3% of the value in “25C,” mean ± S.E.M.). In conclusion, a similar inotropic effect can be observed in rat ventricular myocardium under totally different kinetics of free cytosolic calcium. The extent of LDA is not determined by actual peak systolic tension but is regulated by the level of peak systolic calcium and the kinetics of Ca-transient decline which, in turn, are governed by Ca-TnC dissociation and Ca2+ reuptake by the sarcoplasmic reticulum. Altogether, these findings constitute new evidence about the role of the length-dependent modulation of Ca2+ homeostasis in the mechanisms of calcium regulation of contraction and mechano-calcium feedback in the myocardium. © Copyright © 2019 Lookin and Protsenko. Russian Foundation for Basic Research, RFBR: 18-04-00572-a The study was carried out within the framework of the IIF UrB RAS theme No АААА-А18-118020590031-8, supported by RFBR (grant #18-04-00572-a) and by RF Government Act #211 of March 16, 2013 (agreement 02.A03.21.0006).
Databáze: OpenAIRE
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