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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

Normalized calcium transient amplitude during changes in pacing frequency. (a) Average relative calcium amplitude (n = 6) during the transition from 1 Hz to 4 Hz. Maximal and minimal calcium transient amplitudes were averaged for 5 seconds prior to the 4 Hz change in frequency, at the 1-, 2-, 3-, 4-, 5-, and 60-second time points following the frequency switch to 4 Hz. ∗ represents statistical significance from 5-second prior value and ψ represent statistical significance from 60-second value, P < 0.05. (b) Average relative maximal and minimal calcium transient amplitude recorded at 1 second prior to the 1 Hz frequency change and at 5, 10, 15, 20, and 60 seconds during the 1 Hz stabilization process (n = 4). ∗ represents a statistical significance from 1 second prior values. A P < 0.05 is considered significant.
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fig6: Normalized calcium transient amplitude during changes in pacing frequency. (a) Average relative calcium amplitude (n = 6) during the transition from 1 Hz to 4 Hz. Maximal and minimal calcium transient amplitudes were averaged for 5 seconds prior to the 4 Hz change in frequency, at the 1-, 2-, 3-, 4-, 5-, and 60-second time points following the frequency switch to 4 Hz. ∗ represents statistical significance from 5-second prior value and ψ represent statistical significance from 60-second value, P < 0.05. (b) Average relative maximal and minimal calcium transient amplitude recorded at 1 second prior to the 1 Hz frequency change and at 5, 10, 15, 20, and 60 seconds during the 1 Hz stabilization process (n = 4). ∗ represents a statistical significance from 1 second prior values. A P < 0.05 is considered significant.

Mentions: Averages of the calcium transient alterations from 1 to 4 Hz show a drastic increase in the diastolic calcium level not necessarily due to changes in end twitch calcium levels (Figure 6(a)). The averages were taken at 5 seconds prior to the frequency change and at subsequent time points after the change in frequency. Additionally, once the muscle is stabilized (60-second time point), the end twitch and peak calcium levels are at their highest, as compared to all other earlier time points. To determine the effect of decreasing frequency on calcium transient, we examined the alterations in end twitch and peak calcium amplitude during the transition from 4 Hz to 1 Hz. In Figure 6(b), we looked at 4 beats (or 1 second) prior to the change in frequency, followed by 5, 10, 15, 20, and 60 seconds after the change to 1 Hz. During these times the functional changes during the frequency transition can be visualized and can thus be compared to the contractile function at steady-state. Once again we used the 60-second time point as a representative of the stabilized force and calcium transient amplitude. Here, we are able to show that with decreases in frequency there is a decline in end twitch and peak calcium amplitude maintained until the muscle has stabilized.


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)

Normalized calcium transient amplitude during changes in pacing frequency. (a) Average relative calcium amplitude (n = 6) during the transition from 1 Hz to 4 Hz. Maximal and minimal calcium transient amplitudes were averaged for 5 seconds prior to the 4 Hz change in frequency, at the 1-, 2-, 3-, 4-, 5-, and 60-second time points following the frequency switch to 4 Hz. ∗ represents statistical significance from 5-second prior value and ψ represent statistical significance from 60-second value, P < 0.05. (b) Average relative maximal and minimal calcium transient amplitude recorded at 1 second prior to the 1 Hz frequency change and at 5, 10, 15, 20, and 60 seconds during the 1 Hz stabilization process (n = 4). ∗ represents a statistical significance from 1 second prior values. A P < 0.05 is considered significant.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4413957&req=5

fig6: Normalized calcium transient amplitude during changes in pacing frequency. (a) Average relative calcium amplitude (n = 6) during the transition from 1 Hz to 4 Hz. Maximal and minimal calcium transient amplitudes were averaged for 5 seconds prior to the 4 Hz change in frequency, at the 1-, 2-, 3-, 4-, 5-, and 60-second time points following the frequency switch to 4 Hz. ∗ represents statistical significance from 5-second prior value and ψ represent statistical significance from 60-second value, P < 0.05. (b) Average relative maximal and minimal calcium transient amplitude recorded at 1 second prior to the 1 Hz frequency change and at 5, 10, 15, 20, and 60 seconds during the 1 Hz stabilization process (n = 4). ∗ represents a statistical significance from 1 second prior values. A P < 0.05 is considered significant.
Mentions: Averages of the calcium transient alterations from 1 to 4 Hz show a drastic increase in the diastolic calcium level not necessarily due to changes in end twitch calcium levels (Figure 6(a)). The averages were taken at 5 seconds prior to the frequency change and at subsequent time points after the change in frequency. Additionally, once the muscle is stabilized (60-second time point), the end twitch and peak calcium levels are at their highest, as compared to all other earlier time points. To determine the effect of decreasing frequency on calcium transient, we examined the alterations in end twitch and peak calcium amplitude during the transition from 4 Hz to 1 Hz. In Figure 6(b), we looked at 4 beats (or 1 second) prior to the change in frequency, followed by 5, 10, 15, 20, and 60 seconds after the change to 1 Hz. During these times the functional changes during the frequency transition can be visualized and can thus be compared to the contractile function at steady-state. Once again we used the 60-second time point as a representative of the stabilized force and calcium transient amplitude. Here, we are able to show that with decreases in frequency there is a decline in end twitch and peak calcium amplitude maintained until the muscle has stabilized.

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