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Effects of membrane depolarization and changes in extracellular [K(+)] on the Ca (2+) transients of fast skeletal muscle fibers. Implications for muscle fatigue.

Quiñonez M, González F, Morgado-Valle C, DiFranco M - J. Muscle Res. Cell. Motil. (2010)

Bottom Line: Similar effects were found for the Ca(2+) transients elicited by the first pulse of 100 Hz trains.Changes in Ca(2+) transients along the trains were associated with impaired or abortive APs.The effects of 10 mM K(+)(O) on Ca(2+) transients, but not those of 15 mM K(+)(O), could be fully reversed by hyperpolarization.

View Article: PubMed Central - PubMed

Affiliation: Laboratorio de Fisiología y Biofisíca del Músculo, IBE, UCV, Caracas, Venezuela. mquinonez@mednet.ucla.edu

ABSTRACT
Repetitive activation of skeletal muscle fibers leads to a reduced transmembrane K(+) gradient. The resulting membrane depolarization has been proposed to play a major role in the onset of muscle fatigue. Nevertheless, raising the extracellular K(+) K(+)(O) concentration ([K(+)](O)) to 10 mM potentiates twitch force of rested amphibian and mammalian fibers. We used a double Vaseline gap method to simultaneously record action potentials (AP) and Ca(2+) transients from rested frog fibers activated by single and tetanic stimulation (10 pulses, 100 Hz) at various [K(+)](O) and membrane potentials. Depolarization resulting from current injection or raised [K(+](O) produced an increase in the resting [Ca(2+)]. Ca(2+) transients elicited by single stimulation were potentiated by depolarization from -80 to -60 mV but markedly depressed by further depolarization. Potentiation was inversely correlated with a reduction in the amplitude, overshoot and duration of APs. Similar effects were found for the Ca(2+) transients elicited by the first pulse of 100 Hz trains. Depression or block of Ca(2+) transient in response to the 2nd to 10th pulses of 100 Hz trains was observed at smaller depolarizations as compared to that seen when using single stimulation. Changes in Ca(2+) transients along the trains were associated with impaired or abortive APs. Raising [K(+)](O) to 10 mM potentiated Ca(2+) transients elicited by single and tetanic stimulation, while raising [K(+)](O) to 15 mM markedly depressed both responses. The effects of 10 mM K(+)(O) on Ca(2+) transients, but not those of 15 mM K(+)(O), could be fully reversed by hyperpolarization. The results suggests that the force potentiating effects of 10 mM K(+)(O) might be mediated by depolarization dependent changes in resting [Ca(2+)] and Ca(2+) release, and that additional mechanisms might be involved in the effects of 15 mM K(+)(O) on force generation.

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Effect of holding potential on free resting [Ca2+] calculated from OGB-5N (A–C) and Fluo-3 data (D–F). Traces 1–5 in A, B and D, E are the resting [Ca2+] recorded at: −100 (control), −80, −70, −60 and −55 mV, respectively. Trace 6 is the resting [Ca2+] recorded 3 min after repolarization to −100 mV. C and F are the average resting [Ca2+] as a function of membrane potential from 8 to 6 fibers, respectively. [OGB-5N]: 200 μM. [Fluo-3]: 100 μM. Sarcomere length: 4.3 ± 0.2 μm and 4.1 ± 0.3 μm for C and F, respectively. Records were taken ~3 min after changing membrane potential
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Fig3: Effect of holding potential on free resting [Ca2+] calculated from OGB-5N (A–C) and Fluo-3 data (D–F). Traces 1–5 in A, B and D, E are the resting [Ca2+] recorded at: −100 (control), −80, −70, −60 and −55 mV, respectively. Trace 6 is the resting [Ca2+] recorded 3 min after repolarization to −100 mV. C and F are the average resting [Ca2+] as a function of membrane potential from 8 to 6 fibers, respectively. [OGB-5N]: 200 μM. [Fluo-3]: 100 μM. Sarcomere length: 4.3 ± 0.2 μm and 4.1 ± 0.3 μm for C and F, respectively. Records were taken ~3 min after changing membrane potential

Mentions: Here we found an intriguing effect of membrane depolarization on resting [Ca2+]. Figure 3 show that stepwise membrane depolarization from −100 to −55 mV is associated with a graduated and reversible increase in resting [Ca2+]. Analysis of OGB-5N data (Fig. 3A, B) show that at −55 mV free [Ca2+] is about threefold that assumed in quiescent polarized fibers (100 nM, see Methods), and that fiber repolarization to −100 mV results in the reversal of those effects (Fig. 3B). Similar results were obtained using Fluo-3 (Fig. 3D, E), but calculated [Ca2+] changes were larger than those calculated from OGB-5N data. Since in steady-state conditions both dyes are expected to report similar values of [Ca2+], the differences found probably reflect inadequacies of the dyes parameters. Panels C and F in Fig. 3 show pooled data obtained from fibers loaded with OGB-5N or Fluo-3, respectively.Fig. 3


Effects of membrane depolarization and changes in extracellular [K(+)] on the Ca (2+) transients of fast skeletal muscle fibers. Implications for muscle fatigue.

Quiñonez M, González F, Morgado-Valle C, DiFranco M - J. Muscle Res. Cell. Motil. (2010)

Effect of holding potential on free resting [Ca2+] calculated from OGB-5N (A–C) and Fluo-3 data (D–F). Traces 1–5 in A, B and D, E are the resting [Ca2+] recorded at: −100 (control), −80, −70, −60 and −55 mV, respectively. Trace 6 is the resting [Ca2+] recorded 3 min after repolarization to −100 mV. C and F are the average resting [Ca2+] as a function of membrane potential from 8 to 6 fibers, respectively. [OGB-5N]: 200 μM. [Fluo-3]: 100 μM. Sarcomere length: 4.3 ± 0.2 μm and 4.1 ± 0.3 μm for C and F, respectively. Records were taken ~3 min after changing membrane potential
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2908756&req=5

Fig3: Effect of holding potential on free resting [Ca2+] calculated from OGB-5N (A–C) and Fluo-3 data (D–F). Traces 1–5 in A, B and D, E are the resting [Ca2+] recorded at: −100 (control), −80, −70, −60 and −55 mV, respectively. Trace 6 is the resting [Ca2+] recorded 3 min after repolarization to −100 mV. C and F are the average resting [Ca2+] as a function of membrane potential from 8 to 6 fibers, respectively. [OGB-5N]: 200 μM. [Fluo-3]: 100 μM. Sarcomere length: 4.3 ± 0.2 μm and 4.1 ± 0.3 μm for C and F, respectively. Records were taken ~3 min after changing membrane potential
Mentions: Here we found an intriguing effect of membrane depolarization on resting [Ca2+]. Figure 3 show that stepwise membrane depolarization from −100 to −55 mV is associated with a graduated and reversible increase in resting [Ca2+]. Analysis of OGB-5N data (Fig. 3A, B) show that at −55 mV free [Ca2+] is about threefold that assumed in quiescent polarized fibers (100 nM, see Methods), and that fiber repolarization to −100 mV results in the reversal of those effects (Fig. 3B). Similar results were obtained using Fluo-3 (Fig. 3D, E), but calculated [Ca2+] changes were larger than those calculated from OGB-5N data. Since in steady-state conditions both dyes are expected to report similar values of [Ca2+], the differences found probably reflect inadequacies of the dyes parameters. Panels C and F in Fig. 3 show pooled data obtained from fibers loaded with OGB-5N or Fluo-3, respectively.Fig. 3

Bottom Line: Similar effects were found for the Ca(2+) transients elicited by the first pulse of 100 Hz trains.Changes in Ca(2+) transients along the trains were associated with impaired or abortive APs.The effects of 10 mM K(+)(O) on Ca(2+) transients, but not those of 15 mM K(+)(O), could be fully reversed by hyperpolarization.

View Article: PubMed Central - PubMed

Affiliation: Laboratorio de Fisiología y Biofisíca del Músculo, IBE, UCV, Caracas, Venezuela. mquinonez@mednet.ucla.edu

ABSTRACT
Repetitive activation of skeletal muscle fibers leads to a reduced transmembrane K(+) gradient. The resulting membrane depolarization has been proposed to play a major role in the onset of muscle fatigue. Nevertheless, raising the extracellular K(+) K(+)(O) concentration ([K(+)](O)) to 10 mM potentiates twitch force of rested amphibian and mammalian fibers. We used a double Vaseline gap method to simultaneously record action potentials (AP) and Ca(2+) transients from rested frog fibers activated by single and tetanic stimulation (10 pulses, 100 Hz) at various [K(+)](O) and membrane potentials. Depolarization resulting from current injection or raised [K(+](O) produced an increase in the resting [Ca(2+)]. Ca(2+) transients elicited by single stimulation were potentiated by depolarization from -80 to -60 mV but markedly depressed by further depolarization. Potentiation was inversely correlated with a reduction in the amplitude, overshoot and duration of APs. Similar effects were found for the Ca(2+) transients elicited by the first pulse of 100 Hz trains. Depression or block of Ca(2+) transient in response to the 2nd to 10th pulses of 100 Hz trains was observed at smaller depolarizations as compared to that seen when using single stimulation. Changes in Ca(2+) transients along the trains were associated with impaired or abortive APs. Raising [K(+)](O) to 10 mM potentiated Ca(2+) transients elicited by single and tetanic stimulation, while raising [K(+)](O) to 15 mM markedly depressed both responses. The effects of 10 mM K(+)(O) on Ca(2+) transients, but not those of 15 mM K(+)(O), could be fully reversed by hyperpolarization. The results suggests that the force potentiating effects of 10 mM K(+)(O) might be mediated by depolarization dependent changes in resting [Ca(2+)] and Ca(2+) release, and that additional mechanisms might be involved in the effects of 15 mM K(+)(O) on force generation.

Show MeSH
Related in: MedlinePlus