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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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Ca2+ transients elicited by single stimulation in a fiber exposed to 10 mM extracellular K+. A Superimposed Ca2+ transients calculated from fluorescence transients recorded in control conditions (−100 mV, 2.5 mM , trace 1), after depolarizing the fiber to −70 mV by current injection (2.5 mM , trace 2), and after exposing the fiber to 10 mM  (trace 3). B Traces 1–3 are the APs corresponding to data in A. C Ca2+ transients recorded at −100 mV in a fiber exposed to 2.5 mM  (trace 1) and 10 mM  (trace 2). D Traces 1–2 are the APs corresponding to data in panel C. The dashed lines in B and D indicate the zero potential. Sarcomere length: 4.3 μm. Records were taken about 20 min after changing solutions
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Fig7: Ca2+ transients elicited by single stimulation in a fiber exposed to 10 mM extracellular K+. A Superimposed Ca2+ transients calculated from fluorescence transients recorded in control conditions (−100 mV, 2.5 mM , trace 1), after depolarizing the fiber to −70 mV by current injection (2.5 mM , trace 2), and after exposing the fiber to 10 mM (trace 3). B Traces 1–3 are the APs corresponding to data in A. C Ca2+ transients recorded at −100 mV in a fiber exposed to 2.5 mM (trace 1) and 10 mM (trace 2). D Traces 1–2 are the APs corresponding to data in panel C. The dashed lines in B and D indicate the zero potential. Sarcomere length: 4.3 μm. Records were taken about 20 min after changing solutions

Mentions: The effects of potassium accumulation during fatigue were tested independently from other factors by measuring Ca2+ transients and AP’s in rested fibers exposed to 10 and 15 mM . We first studied the effect of raising the to 10 mM on the Ca2+ transients elicited by single stimulation (Fig. 7). Fibers depolarized to about −70 mV when exposed to 10 mM . Ca2+ transients calculated from fluorescence transients recorded in 10 mM (Fig. 7A, trace 3) are potentiated and prolonged as compared to those obtained from data recorded in normal Ringer at −100 mV (trace 1). Also it can be seen that resting [Ca2+] is higher in high (trace 3) than in normal Ringer (trace 1). This result is in agreement with the relationship between resting [Ca2+] and the resting membrane potential described above. Since fibers exposed to 10 mM extracellular K+ depolarizes to approximately −70 mV (Fig. 7B, trace 3), in Fig. 7A the Ca2+ transient obtained in a fibers maintained in normal Ringer but depolarized to −70 mV by current injection (trace 2) is included for comparison. It can be seen that both transients are very similar. The corresponding AP’s (Fig. 6B, traces 2–3, respectively) are also comparable. The fact that K+-induced depolarization has similar effects to those of depolarization induced by current injection is the first direct evidence suggesting that the effects of 10 mM on Ca2+ transients shown here and the effects on active force production shown elsewhere (Renaud and Light 1992; Bouclin et al. 1995; Cairns et al. 1997) are due to the depolarization of the membrane, and, more importantly, possibly mediated by a potentiation of Ca2+ release, i.e., they are not due to the presence of K+ per se. Further evidence in support of this possibility is provided in Fig. 7C, which shows that the effects of 10 mM can be reversed by repolarizing the fiber by means of current injection. As can be seen the Ca2+ transient obtained at −100 mV in the presence of 10 mM is almost identical to that obtained in control conditions (−100 mV, 2.5 mM , Fig. 7C, trace 2). Also, as shown above, the increased resting [Ca2+] in the presence of 10 mM is reversed by repolarization. Correspondingly, Fig. 7D shows that AP’s eliciting the transients in Fig. 7C do not differ significantly, despite being recorded in the presence of different . Results presented in Fig. 7 were obtained from a fiber that showed one of the largest depolarization-induced potentiation of Ca2+ release.Fig. 7


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)

Ca2+ transients elicited by single stimulation in a fiber exposed to 10 mM extracellular K+. A Superimposed Ca2+ transients calculated from fluorescence transients recorded in control conditions (−100 mV, 2.5 mM , trace 1), after depolarizing the fiber to −70 mV by current injection (2.5 mM , trace 2), and after exposing the fiber to 10 mM  (trace 3). B Traces 1–3 are the APs corresponding to data in A. C Ca2+ transients recorded at −100 mV in a fiber exposed to 2.5 mM  (trace 1) and 10 mM  (trace 2). D Traces 1–2 are the APs corresponding to data in panel C. The dashed lines in B and D indicate the zero potential. Sarcomere length: 4.3 μm. Records were taken about 20 min after changing solutions
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Fig7: Ca2+ transients elicited by single stimulation in a fiber exposed to 10 mM extracellular K+. A Superimposed Ca2+ transients calculated from fluorescence transients recorded in control conditions (−100 mV, 2.5 mM , trace 1), after depolarizing the fiber to −70 mV by current injection (2.5 mM , trace 2), and after exposing the fiber to 10 mM (trace 3). B Traces 1–3 are the APs corresponding to data in A. C Ca2+ transients recorded at −100 mV in a fiber exposed to 2.5 mM (trace 1) and 10 mM (trace 2). D Traces 1–2 are the APs corresponding to data in panel C. The dashed lines in B and D indicate the zero potential. Sarcomere length: 4.3 μm. Records were taken about 20 min after changing solutions
Mentions: The effects of potassium accumulation during fatigue were tested independently from other factors by measuring Ca2+ transients and AP’s in rested fibers exposed to 10 and 15 mM . We first studied the effect of raising the to 10 mM on the Ca2+ transients elicited by single stimulation (Fig. 7). Fibers depolarized to about −70 mV when exposed to 10 mM . Ca2+ transients calculated from fluorescence transients recorded in 10 mM (Fig. 7A, trace 3) are potentiated and prolonged as compared to those obtained from data recorded in normal Ringer at −100 mV (trace 1). Also it can be seen that resting [Ca2+] is higher in high (trace 3) than in normal Ringer (trace 1). This result is in agreement with the relationship between resting [Ca2+] and the resting membrane potential described above. Since fibers exposed to 10 mM extracellular K+ depolarizes to approximately −70 mV (Fig. 7B, trace 3), in Fig. 7A the Ca2+ transient obtained in a fibers maintained in normal Ringer but depolarized to −70 mV by current injection (trace 2) is included for comparison. It can be seen that both transients are very similar. The corresponding AP’s (Fig. 6B, traces 2–3, respectively) are also comparable. The fact that K+-induced depolarization has similar effects to those of depolarization induced by current injection is the first direct evidence suggesting that the effects of 10 mM on Ca2+ transients shown here and the effects on active force production shown elsewhere (Renaud and Light 1992; Bouclin et al. 1995; Cairns et al. 1997) are due to the depolarization of the membrane, and, more importantly, possibly mediated by a potentiation of Ca2+ release, i.e., they are not due to the presence of K+ per se. Further evidence in support of this possibility is provided in Fig. 7C, which shows that the effects of 10 mM can be reversed by repolarizing the fiber by means of current injection. As can be seen the Ca2+ transient obtained at −100 mV in the presence of 10 mM is almost identical to that obtained in control conditions (−100 mV, 2.5 mM , Fig. 7C, trace 2). Also, as shown above, the increased resting [Ca2+] in the presence of 10 mM is reversed by repolarization. Correspondingly, Fig. 7D shows that AP’s eliciting the transients in Fig. 7C do not differ significantly, despite being recorded in the presence of different . Results presented in Fig. 7 were obtained from a fiber that showed one of the largest depolarization-induced potentiation of Ca2+ release.Fig. 7

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