Cardiac contractility is regulated by changes in intracellular Ca concentration (Cai). Normal function requires that Cai be sufficiently high in systole and low in diastole. Much of the Ca needed for ...contraction comes from the sarcoplasmic reticulum and is released by the process of calcium-induced calcium release. The factors that regulate and fine-tune the initiation and termination of release are reviewed. The precise control of intracellular Ca cycling depends on the relationships between the various channels and pumps that are involved. We consider 2 aspects(1) structural couplingthe transporters are organized within the dyad, linking the transverse tubule and sarcoplasmic reticulum and ensuring close proximity of Ca entry to sites of release. (2) Functional couplingwhere the fluxes across all membranes must be balanced such that, in the steady state, Ca influx equals Ca efflux on every beat. The remainder of the review considers specific aspects of Ca signaling, including the role of Ca buffers, mitochondria, Ca leak, and regulation of diastolic Cai.
Purpose
Our previous study showed that one 3-s maximal eccentric contraction a day performed 5 days a week for 4 weeks (5DW) increased maximal voluntary contraction (MVC) strength of the elbow ...flexors more than 10%. The present study examined whether muscle strength would still increase when the frequency was reduced to 2 days or 3 days per week.
Methods
Twenty-six healthy young adults were recruited in the present study and placed to two groups (n = 13/group) based on the weekly frequency of the one 3-s maximal eccentric contraction for two (2DW) or three days per week (3DW) for 4 weeks. Changes in MVC-isometric, MVC-concentric, MVC-eccentric torque of the elbow flexors, and muscle thickness of biceps brachii and brachialis (MT) before and after the 4-week training were compared between 2DW and 3DW groups, and also compared to the 5DW group in the previous study.
Results
The 2DW group showed no significant changes in MVC torque. Significant (P < 0.05) increases in MVC-concentric (2.5 ± 10.4%) and MVC-eccentric (3.9 ± 4.9%) torque were observed for the 3DW group, but the magnitude of the increase was smaller (P < 0.05) than that presented by the 5DW group (12.8 ± 9.6%, 12.2 ± 7.8%). No significant changes in MT were evident for any of the groups.
Conclusion
These results suggest that at least three days a week are necessary for the one 3-s maximal eccentric contraction to be effective for increasing muscle strength, and more frequent sessions in a week (e.g., 5 days) appear to induce greater increases in muscle strength.
RATIONALE:Myocardial delivery of human mesenchymal stem cells (hMSCs) is an emerging therapy for treating the failing heart. However, the relative effects of hMSC-mediated heterocellular coupling ...(HC) and paracrine signaling (PS) on human cardiac contractility and arrhythmogenicity remain unresolved.
OBJECTIVE:The objective is to better understand hMSC PS and HC effects on human cardiac contractility and arrhythmogenicity by integrating experimental and computational approaches.
METHODS AND RESULTS:Extending our previous hMSC–cardiomyocyte HC computational model, we incorporated experimentally calibrated hMSC PS effects on cardiomyocyte L-type calcium channel/sarcoendoplasmic reticulum calcium-ATPase activity and cardiac tissue fibrosis. Excitation–contraction simulations of hMSC PS-only and combined HC+PS effects on human cardiomyocytes were representative of human engineered cardiac tissue (hECT) contractile function measurements under matched experimental treatments. Model simulations and hECTs both demonstrated that hMSC-mediated effects were most pronounced under PS-only conditions, where developed force increased ≈4-fold compared with non–hMSC-supplemented controls during physiological 1-Hz pacing. Simulations predicted contractility of isolated healthy and ischemic adult human cardiomyocytes would be minimally sensitive to hMSC HC, driven primarily by PS. Dominance of hMSC PS was also revealed in simulations of fibrotic cardiac tissue, where hMSC PS protected from potential proarrhythmic effects of HC at various levels of engraftment. Finally, to study the nature of the hMSC paracrine effects on contractility, proteomic analysis of hECT/hMSC conditioned media predicted activation of PI3K/Akt signaling, a recognized target of both soluble and exosomal fractions of the hMSC secretome. Treating hECTs with exosome-enriched, but not exosome-depleted, fractions of the hMSC secretome recapitulated the effects observed with hMSC conditioned media on hECT-developed force and expression of calcium-handling genes (eg, SERCA2a, L-type calcium channel).
CONCLUSIONS:Collectively, this integrated experimental and computational study helps unravel relative hMSC PS and HC effects on human cardiac contractility and arrhythmogenicity, and provides novel insight into the role of exosomes in hMSC paracrine-mediated effects on contractility.
Cardiac excitation‐contraction (E‐C) coupling is influenced by (at least) three dynamic systems that couple and feedback to one another (see Figure). Here we review the mechanical effects on ...cardiomyocytes that include mechano‐electro‐transduction (commonly referred to as mechano‐electric coupling, MEC) and mechano‐chemo‐transduction (MCT) mechanisms at cell and molecular levels which couple to Ca2+‐electro and E‐C coupling reviewed elsewhere. These feedback loops from muscle contraction and mechano‐transduction to the Ca2+ homeodynamics and to the electrical excitation are essential for understanding the E‐C coupling dynamic system and arrhythmogenesis in mechanically loaded hearts. This white paper comprises two parts, each reflecting key aspects from the 2018 UC Davis symposium: MEC (how mechanical load influences electrical dynamics) and MCT (how mechanical load alters cell signalling and Ca2+ dynamics). Of course, such separation is artificial since Ca2+ dynamics profoundly affect ion channels and electrogenic transporters and vice versa. In time, these dynamic systems and their interactions must become fully integrated, and that should be a goal for a comprehensive understanding of how mechanical load influences cell signalling, Ca2+ homeodynamics and electrical dynamics. In this white paper we emphasize current understanding, consensus, controversies and the pressing issues for future investigations. Space constraints make it impossible to cover all relevant articles in the field, so we will focus on the topics discussed at the symposium.
figure legend Cardiac excitation‐contraction coupling and feedback pathways by mechano‐electro‐ and mechano‐chemo‐transduction.
During the last two decades the concept of F-contraction, its modifications,
extensions and applications, is in the spotlight of scientific research in
the area of Metric Fixed Point Theory. It is ...natural to ask what is the
relation between the newly introduced F-contraction and some well-known
classes of contraction mappings. We will discuss the relation between
F-contraction and some of its modification on one side and Boyd-Wong
contraction or Matkowski contraction on the other. The main aim is to
compare the conditions under which those classes of contractions obtain the
unique fixed point on a complete metric space and to prove under which
assumptions we assert that F-contraction is a Boyd-Wong or Matkowski
contraction.
A geometric generalization of contraction theory called <inline-formula><tex-math notation="LaTeX">k</tex-math></inline-formula>-contraction was recently developed using <inline-formula><tex-math ...notation="LaTeX">k</tex-math></inline-formula>-compound matrices. In this note, we focus on the relations between <inline-formula><tex-math notation="LaTeX">k</tex-math></inline-formula>-contraction and two other generalized contraction frameworks: partial contraction (also known as virtual contraction) and horizontal contraction. We show that in general these three notions of contraction are different. We here provide new sufficient conditions guaranteeing that partial contraction implies horizontal contraction, and that horizontal contraction implies <inline-formula><tex-math notation="LaTeX">k</tex-math></inline-formula>-contraction. We use the Andronov-Hopf oscillator to demonstrate some of the theoretical results.
The present study compared a 3‐s isometric maximal voluntary contraction (MVC), concentric MVC and eccentric MVC of the elbow flexors performed daily for 5 days a week for 4 weeks for changes in ...muscle strength and thickness. Young sedentary individuals were assigned to one of three training groups (n = 13 per group) that performed either 3‐s isometric, concentric, or eccentric MVC once a day for 20 days, or to a control group (n = 10) that had measurements without training. The participants in the isometric group performed isometric MVC at 55° (0.96 rad) elbow flexion, and those in the concentric or eccentric group performed concentric MVC or eccentric MVC between 10° (0.17 rad) and 100° (1.75 rad) elbow flexion at 30°/s (0.52 rad/s) on an isokinetic dynamometer. MVC isometric torque at 20° (0.35 rad), 55° (0.96 rad), and 90° (1.57 rad) elbow flexion, MVC concentric and eccentric torque at 30°/s (0.52 rad/s) and 180°/s (3.14 rad/s), and muscle thickness (MT) of biceps brachii and brachialis were measured before and several days after the 20th exercise session. The control group did not show any changes. The eccentric group showed increases (p < 0.01) in isometric (three angle average: 10.2 ± 6.4%), concentric (two velocity average: 12.8 ± 9.6%), and eccentric MVC torque (12.2 ± 7.8%). An increase (p < 0.05) was limited for isometric MVC torque (6.3 ± 6.0%) in the concentric group, and for eccentric MVC torque (7.2 ± 4.4%) in the isometric group. No significant changes in MT were evident for all groups. Performing one 3‐s MVC a day increased muscle strength, but eccentric MVC produced more potent effects than isometric or concentric MVC.
Excitation‐contraction (EC) coupling in skeletal muscles operates through a physical interaction between the dihydropyridine receptor (DHPR), acting as a voltage sensor, and the ryanodine receptor ...(RyR1), acting as a calcium release channel. Recently, the adaptor protein SH3 and cysteine‐rich containing protein 3 (STAC3) has been identified as a myopathy disease gene and as an additional essential EC coupling component. STAC3 interacts with DHPR sequences including the critical EC coupling domain and has been proposed to function in linking the DHPR and RyR1. However, we and others demonstrated that incorporation of recombinant STAC3 into skeletal muscle triads critically depends only on the DHPR but not the RyR1. On the contrary, here, we provide evidence that endogenous STAC3 incorporates into triads in the absence of the DHPR in myotubes and muscle fibers of dysgenic mice. This finding demonstrates that STAC3 interacts with additional triad proteins and is consistent with its proposed role in directly or indirectly linking the DHPR with the RyR1.
STAC3 has been demonstrated to establish two discrete interactions with the DHPR: its C1 domain interacts with the IQ domain in the C‐terminus, and the SH3‐1 domain interacts with the IPR motif in the II–III loop of the DHPR. Here, we provide evidence of a third, hitherto unidentified, interaction, which anchors STAC3 in the triad junctions independent of the DHPR. Because of the crucial role of STAC3 in excitation‐contraction coupling and because no additional proteins are necessary to restore voltage‐induced calcium release in heterologous cells, STAC3 may thus directly couple the DHPR with the RyR1.
The present paper aims to define three new notions: Θ e -contraction, a Hardy–Rogers-type Θ -contraction, and an interpolative Θ -contraction in the framework of extended b-metric space. Further, ...some fixed point results via these new notions and the study endeavors toward a feasible solution would be suggested for nonlinear Volterra–Fredholm integral equations of certain types, as well as a solution to a nonlinear fractional differential equation of the Caputo type by using the obtained results. It also considers a numerical example to indicate the effectiveness of this new technique.
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