AUTHOR=Wakefield Jane I. , Bell Stephen P. , Palmer Bradley M. 

TITLE=Inorganic phosphate accelerates cardiac myofilament relaxation in response to lengthening

JOURNAL=Frontiers in Physiology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2022.980662

DOI=10.3389/fphys.2022.980662

ISSN=1664-042X

ABSTRACT=Myocardial relaxation in late systole is enhanced by increasing velocities of lengthening. Given that inorganic phosphate (Pi) can rebind to the force-producing myosin enzyme prior to MgADP release and hasten crossbridge detachment, we hypothesized that myocardial relaxation in late systole would be further enhanced by lengthening in the presence of Pi. Wistar rat left ventricular papillary muscles were attached to platinum clips, placed between a force transducer and a length motor at room temperature, and bathed in Krebs solution with 1.8 mM Ca2+ and varying Pi of 0, 1, 2 and 5 mM. Tension transients were elicited by electrical stimulation at 1 Hz. Peak tension was significantly enhanced by Pi: 0.593±0.088 mN.mm-2 at 0 mM Pi and 0.817±0.159 mN.mm-2 at 5 mM Pi (mean±SEM, P<0.01 by repeated measures ANOVA). Maximum rate of tension development (+dP/dt max) normalized to peak tension was significantly enhanced by Pi: 10.9±0.4 s-1 at 0 mM Pi and 13.2±0.5 s-1 at 5 mM Pi (P<0.05). All temporal characteristics of the force transient were significantly shortened with increasing Pi, e.g., time-to-50% recovery was shortened from 305±14 ms at 0 mM Pi to 256±10 ms at 5 mM Pi (P<0.01). A 1% lengthening stretch with varying duration of 10-200 ms was applied at time-to-50% recovery during the descending phase of the force transient. Matching lengthening stretches were also applied when the muscle was not stimulated, thus providing a control for the passive viscoelastic response. After subtracting the passive from the active force response, the resulting myofilament response demonstrated features of faster myofilament relaxation in response to the stretch. For example, time-to-70% relaxation with 100 ms lengthening duration was shortened by 8.8±6.8 ms at 0 Pi, 19.6±4.8* ms at 1 mM Pi, 31.0±5.6* ms at 2 Pi, and 25.6±5.3* ms at 5 mM Pi (*P<0.01 compared to no change). Our findings suggest that increasing Pi availability at the myofilaments contributes directly to myofilament relaxation due to reversal of the myosin power stroke and especially as the myocardium transitions from late-systole to early-diastole.