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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

Line-scans of a Rhod-2 AM loaded isolated trabecula and changes in calcium amplitude during changes in pacing frequency from 1 Hz to 4 Hz and 4 Hz to 1 Hz. (a) Representative image of matrix line-scan of Rhod-2 AM loaded, isolated muscle, during frequency change from 1 Hz to 4 Hz and corresponding change (b) in calcium transient amplitude (ΔF/Fo). Representative image of line-scan of Rhod-2 AM loaded isolated muscle (c) during frequency change from 4 Hz to 1 Hz and corresponding calcium transient amplitude trace (d) (ΔF/Fo).
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fig5: Line-scans of a Rhod-2 AM loaded isolated trabecula and changes in calcium amplitude during changes in pacing frequency from 1 Hz to 4 Hz and 4 Hz to 1 Hz. (a) Representative image of matrix line-scan of Rhod-2 AM loaded, isolated muscle, during frequency change from 1 Hz to 4 Hz and corresponding change (b) in calcium transient amplitude (ΔF/Fo). Representative image of line-scan of Rhod-2 AM loaded isolated muscle (c) during frequency change from 4 Hz to 1 Hz and corresponding calcium transient amplitude trace (d) (ΔF/Fo).

Mentions: Confocal fluorescent microscopy line-scans of isolated trabeculae loaded with Rhod-2 AM (Figures 5(a) and 5(c)) show the changes in calcium transient in conjunction with changes in pacing frequency from 1 Hz to 4 Hz and 4 Hz to 1 Hz. Figures 5(b) and 5(d) depict these changes in a graphical representation of the microscopy line-scans. As the frequency is increased from 1 Hz to 4 Hz, the first beat is characterized by a depression of calcium transient amplitude due to incomplete SR reloading, followed by a gradual increase in the amplitude of the calcium transient along with an increase in peak twitch and end twitch calcium level. Analysis of ΔF/Fo show an immediate increase in diastolic calcium levels and a gradual increase in end twitch calcium levels (Figure 5(b)). Following a decrease in the frequency of pacing (from 4 Hz to 1 Hz), there is an immediate decline in the diastolic calcium level as well as in the end twitch calcium level (Figure 5(d)).


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)

Line-scans of a Rhod-2 AM loaded isolated trabecula and changes in calcium amplitude during changes in pacing frequency from 1 Hz to 4 Hz and 4 Hz to 1 Hz. (a) Representative image of matrix line-scan of Rhod-2 AM loaded, isolated muscle, during frequency change from 1 Hz to 4 Hz and corresponding change (b) in calcium transient amplitude (ΔF/Fo). Representative image of line-scan of Rhod-2 AM loaded isolated muscle (c) during frequency change from 4 Hz to 1 Hz and corresponding calcium transient amplitude trace (d) (ΔF/Fo).
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig5: Line-scans of a Rhod-2 AM loaded isolated trabecula and changes in calcium amplitude during changes in pacing frequency from 1 Hz to 4 Hz and 4 Hz to 1 Hz. (a) Representative image of matrix line-scan of Rhod-2 AM loaded, isolated muscle, during frequency change from 1 Hz to 4 Hz and corresponding change (b) in calcium transient amplitude (ΔF/Fo). Representative image of line-scan of Rhod-2 AM loaded isolated muscle (c) during frequency change from 4 Hz to 1 Hz and corresponding calcium transient amplitude trace (d) (ΔF/Fo).
Mentions: Confocal fluorescent microscopy line-scans of isolated trabeculae loaded with Rhod-2 AM (Figures 5(a) and 5(c)) show the changes in calcium transient in conjunction with changes in pacing frequency from 1 Hz to 4 Hz and 4 Hz to 1 Hz. Figures 5(b) and 5(d) depict these changes in a graphical representation of the microscopy line-scans. As the frequency is increased from 1 Hz to 4 Hz, the first beat is characterized by a depression of calcium transient amplitude due to incomplete SR reloading, followed by a gradual increase in the amplitude of the calcium transient along with an increase in peak twitch and end twitch calcium level. Analysis of ΔF/Fo show an immediate increase in diastolic calcium levels and a gradual increase in end twitch calcium levels (Figure 5(b)). Following a decrease in the frequency of pacing (from 4 Hz to 1 Hz), there is an immediate decline in the diastolic calcium level as well as in the end twitch calcium level (Figure 5(d)).

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