Adjustments in the force-frequency relationship during passive and exercise-induced hyperthermia

2014 ◽  
Vol 50 (5) ◽  
pp. 822-829 ◽  
Author(s):  
Julien D. Périard ◽  
Sebastien Racinais ◽  
Martin W. Thompson
2017 ◽  
Vol 30 (8) ◽  
pp. 797-806 ◽  
Author(s):  
Silvia V. Alvarez ◽  
Etienne Fortin-Pellerin ◽  
Mohammed Alhabdan ◽  
Jesus S. Lomelin ◽  
Michal Kantoch ◽  
...  

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Heather B Hayes ◽  
Anthony M Nicolini ◽  
Colin Arrowood ◽  
Daniel Millard

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have significantly advanced in vitro cardiac safety and disese modeling, yet remain an immature representation of human myocytes. Electrical or mechanical conditioning of hiPSC-CMs facilitates functional maturation, as measured by a positive force-frequency relationship, but current in vitro protocols require 2-4 weeks of conditioning. Using array-based contractility and local electrical stimulation, we detected functionally mature phenotypes and compound responses in hiPSC-CMs after only 48 hours of chronic pacing. To mature cardiomyocytes, hiPSC-CMs were cultured on 24- and 96-well MEA plates with a dedicated stimulation electrodes. Later, hiPSC-CMs were electrically or optically paced at 2Hz for 48 hours. Multimodal measures quantified contractile and electrophysiological responses to varied pacing rates and compound addition. After 48 hours of pacing, hiPSC-CMs displayed shortened repolarization timing compared to before chronic pacing (baseline: 423 +/- 21 ms; matured: 316 +/- 15 ms), without significant beat period changes (baseline: 1255 +/- 40 ms; matured: 1314 +/- 84 ms). Contractile beat amplitude was measured using array-based impedance during spontaneous beating and at increasing pacing rates (1, 1.2, 1.5, 2, and 2.5 Hz). Before chronic pacing, beat amplitude decreased with increasing pacing rate; after chronic pacing, the same wells displayed increased beat amplitudes with increasing pacing rate. The matured wells also showed enhanced sensitivity to positive inotropes, such as isoproterenol, digoxin, omecamtiv mecarbil, and dobutamine. Local extracellular action potentials (LEAP) further revealed altered electrophysiological response to ranolazine, a multichannel blocker. Unpaced control wells exhibited dose-dependent APD90 prolongation in response to ranolazine, whereas matured wells showed no APD90 change. Similar results were seen with 48 hour of optogenetic pacing at 2 Hz. Overall, hiPSC-CMs chronically paced for only 48 hours exhibited more mature functional phenotypes, including a positive force-frequnecy relationship, enhanced ionotrope sensitivity, and altered compound response.


1996 ◽  
Vol 166 (2) ◽  
pp. 150-155 ◽  
Author(s):  
P. Szigligeti ◽  
C. Pankucsi ◽  
T. B�ny�sz ◽  
A. Varr� ◽  
P. P. N�n�si

Author(s):  
Anne Tiedemann ◽  
Catherine Sherrington ◽  
Daina L. Sturnieks ◽  
Stephen R. Lord ◽  
Mark W. Rogers ◽  
...  

2000 ◽  
Vol 4 (1) ◽  
pp. 43-49 ◽  
Author(s):  
RAMAKRISHNAN Y. NAGARAJ ◽  
CHRISTOPHER M. NOSEK ◽  
MARCO A. P. BROTTO ◽  
MIYUKI NISHI ◽  
HIROSHI TAKESHIMA ◽  
...  

Mitsugumin 29 (MG29), a major protein component of the triad junction in skeletal muscle, has been identified to play roles in the formation of precise junctional membrane structures important for efficient signal conversion in excitation-contraction (E-C) coupling. We carried out several experiments to not only study the role of MG29 in normal muscle contraction but also to determine its role in muscle fatigue. We compared the in vitro contractile properties of three muscles types, extensor digitorum longus (EDL) (fast-twitch muscle), soleus (SOL) (slow-twitch muscle), and diaphragm (DPH) (mixed-fiber muscle), isolated from mice lacking the MG29 gene and wild-type mice prior to and after fatigue. Our results indicate that the mutant EDL and SOL muscles, but not DPH, are more susceptible to fatigue than the wild-type muscles. The mutant muscles not only fatigued to a greater extent but also recovered significantly less than the wild-type muscles. Following fatigue, the mutant EDL and SOL muscles produced lower twitch forces than the wild-type muscles; in addition, fatiguing produced a downward shift in the force-frequency relationship in the mutant mice compared with the wild-type controls. Our results indicate that fatiguing affects the E-C components of the mutant EDL and SOL muscles, and the effect of fatigue in these mutant muscles could be primarily due to an alteration in the intracellular Ca homeostasis.


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