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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

Stopped-flow analysis of the off-rate of Calcium from Rhod-2. Single experimental trace of determining the calcium off-rate, determined from a minimum of n = 10 runs in absence (a) or in presence (b) of myofilaments. Stopped-flow experiments were performed at 37°C.
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fig4: Stopped-flow analysis of the off-rate of Calcium from Rhod-2. Single experimental trace of determining the calcium off-rate, determined from a minimum of n = 10 runs in absence (a) or in presence (b) of myofilaments. Stopped-flow experiments were performed at 37°C.

Mentions: In order to ensure that under our experimental conditions, most notably at 37°C, the dye can accurately track the calcium transient, the off-rate of the dye was investigated using a stopped-flow protocol as performed previously [15]. In Figure 4 the results of this verification are depicted in absence (a) and presence (b) of myofilaments.


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)

Stopped-flow analysis of the off-rate of Calcium from Rhod-2. Single experimental trace of determining the calcium off-rate, determined from a minimum of n = 10 runs in absence (a) or in presence (b) of myofilaments. Stopped-flow experiments were performed at 37°C.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig4: Stopped-flow analysis of the off-rate of Calcium from Rhod-2. Single experimental trace of determining the calcium off-rate, determined from a minimum of n = 10 runs in absence (a) or in presence (b) of myofilaments. Stopped-flow experiments were performed at 37°C.
Mentions: In order to ensure that under our experimental conditions, most notably at 37°C, the dye can accurately track the calcium transient, the off-rate of the dye was investigated using a stopped-flow protocol as performed previously [15]. In Figure 4 the results of this verification are depicted in absence (a) and presence (b) of myofilaments.

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