The lack of slow force response in failing rat myocardium: role of stretch-induced modulation of Ca–TnC kinetics

Lookin, Oleg; Protsenko, Yuri

doi:10.1007/s12576-018-0651-3

Cited by 8 publications

(16 citation statements)

References 52 publications

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“…(as in "35C"), in contrast to the previously observed lengthrelated increase in the bump time-to-peak in isometrically contracting muscles (Lookin and Protsenko, 2019).…”

Section: Length-dependent Effect On Ca-transientcontrasting

confidence: 55%

“…For instance, if a putative Ca-TnC interaction is evaluated during a complete twitch, the integral magnitude of the bump is more reliable vs. the bump amplitude, which reflects a momentary Ca-TnC interaction. A promising finding of this study is that a rate of Ca 2+ utilization by TnC in auxotonically contracting cells, indirectly obtained from the bump time-to-peak value, shows rather the opposite length-dependence compared to isometrically contracting muscles (Lookin et al, 2015;Lookin and Protsenko, 2019). This is very likely attributed to the shortening-induced inactivation of contraction: increased amplitude of auxotonic shortening in a pre-stretched cell induces more inactivation and faster release of Ca 2+ from TnC.…”

Section: Length-dependent Effect On Mechanical Response and Ca-transientmentioning

confidence: 71%

“…Briefly, a progressive increase in the length of isometrically contracting rat cardiac muscle is accompanied by a concomitant short-lived component over monotonic decline of its Ca-transient [the so-called "bump" (Jiang et al, 1998;Kentish and Wrzosek, 1998)]. Previously, we showed a length-dependence of the bump extent in isometrically contracting rat trabeculae (Lookin and Protsenko, 2019). This analysis of Ca-transient bump characteristics was implemented in this study as well ( Figure 5A).…”

Section: Length-dependent Effect On Ca-transientmentioning

confidence: 87%

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

Lookin

Protsenko

2019

Front. Physiol.

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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 Ca 2+ 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-topeak, 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 Ca 2+ reuptake by the sarcoplasmic reticulum. Altogether, these findings constitute Lookin and Protsenko Length-Dependent Activation and Ca-Transient

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“…(as in "35C"), in contrast to the previously observed lengthrelated increase in the bump time-to-peak in isometrically contracting muscles (Lookin and Protsenko, 2019).…”

Section: Length-dependent Effect On Ca-transientcontrasting

confidence: 55%

Section: Length-dependent Effect On Mechanical Response and Ca-transientmentioning

confidence: 71%

Section: Length-dependent Effect On Ca-transientmentioning

confidence: 87%

See 1 more Smart Citation

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

Lookin

Protsenko

2019

Front. Physiol.

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“…The electrical and mechanical mechanisms governing the precise and highly organized actions responsible for electrical propagation in the heart are extremely complex, requiring coordinated neural and humoral factors in the healthy and pathological conditions [17][18][19][20][21][22][23][24]. Such regulatory coordination also depends on the developmental changes in the cardiac substrates that are responsible for actions of transcriptional/translational feedback modifications.…”

Section: Discussionmentioning

confidence: 99%

Cardiac specific transcription factor Csx/Nkx2.5 regulates transient-outward K+ channel expression in pluripotent P19 cell-derived cardiomyocytes

et al. 2020

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The homeobox-containing gene Csx/Nkx2.5 codes several cardiac transcription factors and plays a critical role in early cardiogenesis. We investigated the effect of Csx/Nkx2.5 on the expression of cardiac ion channels using P19-derived cardiomyocytes. P19CL6 cells and P19CL6 cells with Csx/Nkx2.5 overexpression (P19CL6-Csx cells) were induced to differentiate into cardiomyocytes by treatment with dimethyl sulfoxide. Action potentials and membrane currents were measured by whole cell patch clamp at different differentiation stage: the early stage (1-5 days after beating had begun) and the late stage (10-15 days after beating). Expression of Csx/Nkx2.5 mRNA was increased as the differentiation stages advanced in both P19CL6 and P19CL6-Csx cells. In action potential configuration, maximal diastolic potentials in P19CL6-Csx cells exhibited more hyperpolarized potential (-64.2 mV) than those in P19CL6 cells (-54.8 mV, p < 0.01) in the early stage. In P19CL6 cells, among 6 different voltage-gated and ligand-operated K + channels expressed during the early stage, the transient-outward K + channel was most predominant. By overexpression of Csx/Nkx2.5, developmental decrease in the transient-outward K + channel was suppressed. Homeobox-containing gene Csx/Nkx2.5 modifies the amount of distinct ionic channels, during differentiation periods, predominantly changing the expression of the transient-outward K + channel.

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“…The electrical and mechanical mechanisms governing the precise and highly organized actions in the heart are extremely complex, requiring coordinated neural and humoral factors in the healthy and pathological conditions [21][22][23][24][25][26][27][28][29][30][31]. Such sophisticated coordination also depends on the developmental changes in the steps of cardiogenesis including the generation of pacemaker potentials [1][2][3][4][5][6][32][33][34].…”

Section: Discussionmentioning

confidence: 99%

Mitogen-activated protein kinase p38 modulates pacemaker ion channels differentiation in P19-derived pluripotent cells

et al. 2020

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Signal regulators during early cardiogenetic differentiation for the cellular automaticity are largely unknown. Our investigations were designed to clarify the role of transcription factors and their modulators in P19-derived cardiomyocytes to the expression of cardiac pacemaker ion channels. Transcription factors Csx/Nkx2.5 and GATA4 but not MEF2C were markedly inhibited by p38 MAP kinase inhibition in a distinct manner; expression but not phosphorylation of GATA4 was reduced by inhibition of p38 MAP kinase actions. In the presence of an ERK1/2,5 inhibitor PD98059 or a JNK MAP kinase inhibitor SP600125, P19 cells successfully differentiated into cardiomyocytes displaying spontaneous beatings with expression of three types of pacemaker ion channels. We demonstrate that acquisition of cellular automaticity and the expression of pacemaker ion channels are regulated by the transcription factors, Csx/Nkx2.5 and GATA4, through intracellular signals including p38 MAP kinase in the process of P19-derived pluripotent cells differentiation into cardiomyocytes.

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The lack of slow force response in failing rat myocardium: role of stretch-induced modulation of Ca–TnC kinetics

Cited by 8 publications

References 52 publications

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

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

Cardiac specific transcription factor Csx/Nkx2.5 regulates transient-outward K+ channel expression in pluripotent P19 cell-derived cardiomyocytes

Mitogen-activated protein kinase p38 modulates pacemaker ion channels differentiation in P19-derived pluripotent cells

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