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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

Kinetic tracings from muscles stimulated from 1 Hz to 4 Hz (n = 35). Developed force (Fdev) increases rapidly and then gradually following an increase in pacing frequency. The switch in frequency is marked by a rapid decline in Fdev at approximately 60 seconds. Time to peak tension (TTP) and time to 50% relaxation (RT50) rapidly decline following an increase from 1 to 4 Hz pacing frequency and stabilize within 20 seconds of the frequency change.
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fig2: Kinetic tracings from muscles stimulated from 1 Hz to 4 Hz (n = 35). Developed force (Fdev) increases rapidly and then gradually following an increase in pacing frequency. The switch in frequency is marked by a rapid decline in Fdev at approximately 60 seconds. Time to peak tension (TTP) and time to 50% relaxation (RT50) rapidly decline following an increase from 1 to 4 Hz pacing frequency and stabilize within 20 seconds of the frequency change.

Mentions: Figure 2 depicts the alterations in contractile force and twitch kinetics that occur during the transition from 1 to 4 Hz. As the muscle continues at a higher pacing frequency the rapid increase in force production that occurs over the first 5–10 seconds (early phase) is followed by a slower phase (~1-2 minutes) in which the developed force gradually increases (late phase) and eventually stabilizes at the new steady-state. As more clearly shown in Figure 1, during the transition to 4 Hz, there is a rapid decline in force production of the 1st beat following a change in stimulation rate followed by a slower further increase until force stabilizes. Twitch kinetics, time to peak tension (TTP), and time from peak tension to 50% relaxation (RT50) measurements show a similar initial phase, but they reach the steady-state level prior to Fdev reaching the new steady-state.


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)

Kinetic tracings from muscles stimulated from 1 Hz to 4 Hz (n = 35). Developed force (Fdev) increases rapidly and then gradually following an increase in pacing frequency. The switch in frequency is marked by a rapid decline in Fdev at approximately 60 seconds. Time to peak tension (TTP) and time to 50% relaxation (RT50) rapidly decline following an increase from 1 to 4 Hz pacing frequency and stabilize within 20 seconds of the frequency change.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: Kinetic tracings from muscles stimulated from 1 Hz to 4 Hz (n = 35). Developed force (Fdev) increases rapidly and then gradually following an increase in pacing frequency. The switch in frequency is marked by a rapid decline in Fdev at approximately 60 seconds. Time to peak tension (TTP) and time to 50% relaxation (RT50) rapidly decline following an increase from 1 to 4 Hz pacing frequency and stabilize within 20 seconds of the frequency change.
Mentions: Figure 2 depicts the alterations in contractile force and twitch kinetics that occur during the transition from 1 to 4 Hz. As the muscle continues at a higher pacing frequency the rapid increase in force production that occurs over the first 5–10 seconds (early phase) is followed by a slower phase (~1-2 minutes) in which the developed force gradually increases (late phase) and eventually stabilizes at the new steady-state. As more clearly shown in Figure 1, during the transition to 4 Hz, there is a rapid decline in force production of the 1st beat following a change in stimulation rate followed by a slower further increase until force stabilizes. Twitch kinetics, time to peak tension (TTP), and time from peak tension to 50% relaxation (RT50) measurements show a similar initial phase, but they reach the steady-state level prior to Fdev reaching the new steady-state.

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