Limits...
Dissociation of Calcium Transients and Force Development following a Change in Stimulation Frequency in Isolated Rabbit Myocardium.

Haizlip KM, Milani-Nejad N, Brunello L, Varian KD, Slabaugh JL, Walton SD, Gyorke S, Davis JP, Biesiadecki BJ, Janssen PM - Biomed Res Int (2015)

Bottom Line: As the heart transitions from one exercise intensity to another, changes in cardiac output occur, which are modulated by alterations in force development and calcium handling.Although the steady-state force-calcium relationship at various heart rates is well investigated, regulation of these processes during transitions in heart rate is poorly understood.We show that a change in steady-state conditions occurs in multiple phases: a rapid phase, which is characterized by a fast change in force production mirrored by a change in calcium transient amplitude, and a slow phase, which follows the rapid phase and occurs as the muscle proceeds to stabilize at the new frequency.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Cell Biology and D. Davis Heart Lung Institute, College of Medicine, The Ohio State University, 304 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210-1218, USA.

ABSTRACT
As the heart transitions from one exercise intensity to another, changes in cardiac output occur, which are modulated by alterations in force development and calcium handling. Although the steady-state force-calcium relationship at various heart rates is well investigated, regulation of these processes during transitions in heart rate is poorly understood. In isolated right ventricular muscle preparations from the rabbit, we investigated the beat-to-beat alterations in force and calcium during the transition from one stimulation frequency to another, using contractile assessments and confocal microscopy. We show that a change in steady-state conditions occurs in multiple phases: a rapid phase, which is characterized by a fast change in force production mirrored by a change in calcium transient amplitude, and a slow phase, which follows the rapid phase and occurs as the muscle proceeds to stabilize at the new frequency. This second/late phase is characterized by a quantitative dissociation between the calcium transient amplitude and developed force. Twitch timing kinetics, such as time to peak tension and 50% relaxation rate, reached steady-state well before force development and calcium transient amplitude. The dynamic relationship between force and calcium upon a switch in stimulation frequency unveils the dynamic involvement of myofilament-based properties in frequency-dependent activation.

No MeSH data available.


Related in: MedlinePlus

Force and calcium response during twitch after increases in pacing frequency. (a) Overlay of force and calcium tracings normalized to 1 Hz values during the transition from 1 Hz to 4 Hz (approximately 11 seconds). Twitch profiles and calcium transient changes are recorded for every contraction occurring in the trabecula during the brief transition from 1 Hz to 4 Hz. (b) Overlay of force and calcium tracings normalized to 1 Hz values. One twitch at 1 Hz is recorded followed by every twitch that occurs during the 4 Hz stabilization process (60 seconds total). (c) Normalized force tracings overlaid with normalized relative calcium amplitude transients of an individual isolated muscle during a frequency change from 4 Hz to 1 Hz (approximately 20 seconds). Tracings are normalized to 1 Hz stabilized values. (d) Overlay of force and calcium tracings normalized to 1 Hz values. Eight twitches at 4 Hz are recorded followed by every twitch that occurs during the 1 Hz stabilization process (40 seconds total).
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4413957&req=5

fig7: Force and calcium response during twitch after increases in pacing frequency. (a) Overlay of force and calcium tracings normalized to 1 Hz values during the transition from 1 Hz to 4 Hz (approximately 11 seconds). Twitch profiles and calcium transient changes are recorded for every contraction occurring in the trabecula during the brief transition from 1 Hz to 4 Hz. (b) Overlay of force and calcium tracings normalized to 1 Hz values. One twitch at 1 Hz is recorded followed by every twitch that occurs during the 4 Hz stabilization process (60 seconds total). (c) Normalized force tracings overlaid with normalized relative calcium amplitude transients of an individual isolated muscle during a frequency change from 4 Hz to 1 Hz (approximately 20 seconds). Tracings are normalized to 1 Hz stabilized values. (d) Overlay of force and calcium tracings normalized to 1 Hz values. Eight twitches at 4 Hz are recorded followed by every twitch that occurs during the 1 Hz stabilization process (40 seconds total).

Mentions: In order to determine if calcium transient amplitude and Fdev would parallel each other through the early and late stabilization phases, we simultaneously measured Fdev and calcium transient amplitude during our frequency protocols. As shown in Figures 7(a) and 7(b), with increases in frequency there is no significant dissociation between end or peak calcium and Fdev during the early stabilization phase. Surprisingly, when taking an expanded look at the entire stabilization period, a rise in peak and end calcium occurs during the period at which the force has already reached a plateau. This phenomenon is not seen with a decreasing frequency of pacing (Figures 7(c) and 7(d)) suggesting a pertinent role for alterations in myofilament calcium sensitivity during stabilization.


Dissociation of Calcium Transients and Force Development following a Change in Stimulation Frequency in Isolated Rabbit Myocardium.

Haizlip KM, Milani-Nejad N, Brunello L, Varian KD, Slabaugh JL, Walton SD, Gyorke S, Davis JP, Biesiadecki BJ, Janssen PM - Biomed Res Int (2015)

Force and calcium response during twitch after increases in pacing frequency. (a) Overlay of force and calcium tracings normalized to 1 Hz values during the transition from 1 Hz to 4 Hz (approximately 11 seconds). Twitch profiles and calcium transient changes are recorded for every contraction occurring in the trabecula during the brief transition from 1 Hz to 4 Hz. (b) Overlay of force and calcium tracings normalized to 1 Hz values. One twitch at 1 Hz is recorded followed by every twitch that occurs during the 4 Hz stabilization process (60 seconds total). (c) Normalized force tracings overlaid with normalized relative calcium amplitude transients of an individual isolated muscle during a frequency change from 4 Hz to 1 Hz (approximately 20 seconds). Tracings are normalized to 1 Hz stabilized values. (d) Overlay of force and calcium tracings normalized to 1 Hz values. Eight twitches at 4 Hz are recorded followed by every twitch that occurs during the 1 Hz stabilization process (40 seconds total).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4413957&req=5

fig7: Force and calcium response during twitch after increases in pacing frequency. (a) Overlay of force and calcium tracings normalized to 1 Hz values during the transition from 1 Hz to 4 Hz (approximately 11 seconds). Twitch profiles and calcium transient changes are recorded for every contraction occurring in the trabecula during the brief transition from 1 Hz to 4 Hz. (b) Overlay of force and calcium tracings normalized to 1 Hz values. One twitch at 1 Hz is recorded followed by every twitch that occurs during the 4 Hz stabilization process (60 seconds total). (c) Normalized force tracings overlaid with normalized relative calcium amplitude transients of an individual isolated muscle during a frequency change from 4 Hz to 1 Hz (approximately 20 seconds). Tracings are normalized to 1 Hz stabilized values. (d) Overlay of force and calcium tracings normalized to 1 Hz values. Eight twitches at 4 Hz are recorded followed by every twitch that occurs during the 1 Hz stabilization process (40 seconds total).
Mentions: In order to determine if calcium transient amplitude and Fdev would parallel each other through the early and late stabilization phases, we simultaneously measured Fdev and calcium transient amplitude during our frequency protocols. As shown in Figures 7(a) and 7(b), with increases in frequency there is no significant dissociation between end or peak calcium and Fdev during the early stabilization phase. Surprisingly, when taking an expanded look at the entire stabilization period, a rise in peak and end calcium occurs during the period at which the force has already reached a plateau. This phenomenon is not seen with a decreasing frequency of pacing (Figures 7(c) and 7(d)) suggesting a pertinent role for alterations in myofilament calcium sensitivity during stabilization.

Bottom Line: As the heart transitions from one exercise intensity to another, changes in cardiac output occur, which are modulated by alterations in force development and calcium handling.Although the steady-state force-calcium relationship at various heart rates is well investigated, regulation of these processes during transitions in heart rate is poorly understood.We show that a change in steady-state conditions occurs in multiple phases: a rapid phase, which is characterized by a fast change in force production mirrored by a change in calcium transient amplitude, and a slow phase, which follows the rapid phase and occurs as the muscle proceeds to stabilize at the new frequency.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Cell Biology and D. Davis Heart Lung Institute, College of Medicine, The Ohio State University, 304 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210-1218, USA.

ABSTRACT
As the heart transitions from one exercise intensity to another, changes in cardiac output occur, which are modulated by alterations in force development and calcium handling. Although the steady-state force-calcium relationship at various heart rates is well investigated, regulation of these processes during transitions in heart rate is poorly understood. In isolated right ventricular muscle preparations from the rabbit, we investigated the beat-to-beat alterations in force and calcium during the transition from one stimulation frequency to another, using contractile assessments and confocal microscopy. We show that a change in steady-state conditions occurs in multiple phases: a rapid phase, which is characterized by a fast change in force production mirrored by a change in calcium transient amplitude, and a slow phase, which follows the rapid phase and occurs as the muscle proceeds to stabilize at the new frequency. This second/late phase is characterized by a quantitative dissociation between the calcium transient amplitude and developed force. Twitch timing kinetics, such as time to peak tension and 50% relaxation rate, reached steady-state well before force development and calcium transient amplitude. The dynamic relationship between force and calcium upon a switch in stimulation frequency unveils the dynamic involvement of myofilament-based properties in frequency-dependent activation.

No MeSH data available.


Related in: MedlinePlus