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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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Depression of Ca2+ transients in a fiber exposed to 15 mM . A, B Trains of Ca2+ transients obtained in the presence of 2.5 mM extracellular K+ in a fiber polarized to −100 (A) and −70 mV (B). C Ca2+ transients obtained in the same fiber 20 min after exposure to 15 mM extracellular K+. D–F First (1) and last (10) Ca2+ transients of trains in A–C, respectively, shown in an expanded time scale. G–I Trains of APs eliciting the Ca2+ transients in A–C, respectively. J–L First (1) and last APs in G–I shown in an expanded time scale. Dashed lines in A–F indicate the resting [Ca2+]. Dashed lines in G–L indicate resting and zero potential
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Fig9: Depression of Ca2+ transients in a fiber exposed to 15 mM . A, B Trains of Ca2+ transients obtained in the presence of 2.5 mM extracellular K+ in a fiber polarized to −100 (A) and −70 mV (B). C Ca2+ transients obtained in the same fiber 20 min after exposure to 15 mM extracellular K+. D–F First (1) and last (10) Ca2+ transients of trains in A–C, respectively, shown in an expanded time scale. G–I Trains of APs eliciting the Ca2+ transients in A–C, respectively. J–L First (1) and last APs in G–I shown in an expanded time scale. Dashed lines in A–F indicate the resting [Ca2+]. Dashed lines in G–L indicate resting and zero potential

Mentions: Since the [K+] in the t-tubule lumen can reach higher values than those measured in the plasma or tissue fluids (Juel 1986), we measured the Ca2+ release in fibers equilibrated in Ringer containing 15 mM K+. Unexpectedly, fibers exposed to 15 mM depolarized to a similar membrane potential as fibers exposed to 10 mM (−68 ± 1.8 mV; n = 4). Figure 9 compares Ca2+ transients obtained in fibers exposed to 15 mM (panels C and F) with those obtained in the presence of 2.5 mM at −100 and −70 mV (panels A and D; and B and E; respectively). Depolarization of the fibers to a value similar to that observed in the presence of 15 mM K+ resulted in potentiation of Ca2+ transients in response to single (not shown) and repetitive stimulation at 100 Hz (Fig. 9B). Nevertheless, in contrast to what was observed using 10 mM , regardless of its depolarizing effect, no potentiation was observed in the presence of 15 mM . Instead, Ca2+ transients show a monotonic depression along the train, and the depression manifests from the first pulse. By the end of the train (Fig. 9F) the amplitude of Ca2+ transient is about 25% that at the beginning of the train. No alternating amplitudes are seen in this condition, in contrast to that observed in fibers depolarized to −60 mV. As expected, the depression effect of 15 mM on Ca2+ transients is also seen when fibers are stimulated by single pulses. With the caveat that t-tubules have reached a steady state potential in the presence of 15 mM , the data above indicate that depression cannot result only from the depolarization per se, and suggest that potassium ions at this concentration might have another effect. The corresponding records of AP are shown in Fig. 9G–L. The amplitude of the APs in 15 mM is slightly smaller than those in 2.5 mM at −70 mV, and is relatively constant from the second to the last AP along the train. Thus the progressive depression of Ca2+ transients does not correlate with the constancy of the amplitude of the (surface membrane) APs. The FDHM of APs recorded in the presence of 2.5 mM and 15 mM are similar (Fig. 9K, L). The depression of Ca2+ transients elicited by both single and tetanic stimulation seen in fibers exposed to 15 mM is in agreement with the depression of both twitch an tetanic force produced by higher than 10 mM.Fig. 9


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)

Depression of Ca2+ transients in a fiber exposed to 15 mM . A, B Trains of Ca2+ transients obtained in the presence of 2.5 mM extracellular K+ in a fiber polarized to −100 (A) and −70 mV (B). C Ca2+ transients obtained in the same fiber 20 min after exposure to 15 mM extracellular K+. D–F First (1) and last (10) Ca2+ transients of trains in A–C, respectively, shown in an expanded time scale. G–I Trains of APs eliciting the Ca2+ transients in A–C, respectively. J–L First (1) and last APs in G–I shown in an expanded time scale. Dashed lines in A–F indicate the resting [Ca2+]. Dashed lines in G–L indicate resting and zero potential
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Fig9: Depression of Ca2+ transients in a fiber exposed to 15 mM . A, B Trains of Ca2+ transients obtained in the presence of 2.5 mM extracellular K+ in a fiber polarized to −100 (A) and −70 mV (B). C Ca2+ transients obtained in the same fiber 20 min after exposure to 15 mM extracellular K+. D–F First (1) and last (10) Ca2+ transients of trains in A–C, respectively, shown in an expanded time scale. G–I Trains of APs eliciting the Ca2+ transients in A–C, respectively. J–L First (1) and last APs in G–I shown in an expanded time scale. Dashed lines in A–F indicate the resting [Ca2+]. Dashed lines in G–L indicate resting and zero potential
Mentions: Since the [K+] in the t-tubule lumen can reach higher values than those measured in the plasma or tissue fluids (Juel 1986), we measured the Ca2+ release in fibers equilibrated in Ringer containing 15 mM K+. Unexpectedly, fibers exposed to 15 mM depolarized to a similar membrane potential as fibers exposed to 10 mM (−68 ± 1.8 mV; n = 4). Figure 9 compares Ca2+ transients obtained in fibers exposed to 15 mM (panels C and F) with those obtained in the presence of 2.5 mM at −100 and −70 mV (panels A and D; and B and E; respectively). Depolarization of the fibers to a value similar to that observed in the presence of 15 mM K+ resulted in potentiation of Ca2+ transients in response to single (not shown) and repetitive stimulation at 100 Hz (Fig. 9B). Nevertheless, in contrast to what was observed using 10 mM , regardless of its depolarizing effect, no potentiation was observed in the presence of 15 mM . Instead, Ca2+ transients show a monotonic depression along the train, and the depression manifests from the first pulse. By the end of the train (Fig. 9F) the amplitude of Ca2+ transient is about 25% that at the beginning of the train. No alternating amplitudes are seen in this condition, in contrast to that observed in fibers depolarized to −60 mV. As expected, the depression effect of 15 mM on Ca2+ transients is also seen when fibers are stimulated by single pulses. With the caveat that t-tubules have reached a steady state potential in the presence of 15 mM , the data above indicate that depression cannot result only from the depolarization per se, and suggest that potassium ions at this concentration might have another effect. The corresponding records of AP are shown in Fig. 9G–L. The amplitude of the APs in 15 mM is slightly smaller than those in 2.5 mM at −70 mV, and is relatively constant from the second to the last AP along the train. Thus the progressive depression of Ca2+ transients does not correlate with the constancy of the amplitude of the (surface membrane) APs. The FDHM of APs recorded in the presence of 2.5 mM and 15 mM are similar (Fig. 9K, L). The depression of Ca2+ transients elicited by both single and tetanic stimulation seen in fibers exposed to 15 mM is in agreement with the depression of both twitch an tetanic force produced by higher than 10 mM.Fig. 9

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