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Understanding the physiology of the asymptomatic diaphragm of the M1592V hyperkalemic periodic paralysis mouse.

Ammar T, Lin W, Higgins A, Hayward LJ, Renaud JM - J. Gen. Physiol. (2015)

Bottom Line: The improved resting membrane potential (EM) results from significantly increased Na(+) K(+) pump electrogenic activity, and not from an increased protein content.One suggested mechanism for the greater action potential amplitude is lower intracellular Na(+) concentration because of greater Na(+) K(+) pump activity, allowing better Na(+) current during the action potential depolarization phase.Finally, HyperKPP diaphragm had a greater capacity to generate force at depolarized EM compared with wild-type diaphragm.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada.

No MeSH data available.


Related in: MedlinePlus

Ouabain caused greater loss of tetanic force and membrane depolarization in HyperKPP, EDL, and soleus than in diaphragm. (A–C) All muscles were allowed a 30-min equilibrium at 4.7 mM K+ before any measurements or changes in [K+]e or ouabain. For force measurements, muscles were exposed 20 min to ouabain while being exposed to 4.7 mM K+ before [K+]e was increased to 9 mM, still in the presence of ouabain as indicated in the figures. A similar approach was used for resting EM with half the muscles; for the other half, muscles were exposed to ouabain only after [K+]e had been raised to 9 mM K+. The resting EM at 9 mM and 1 µM ouabain was not different between the two approaches, so the data were pooled. Error bars represent SEM; force of five muscles; resting EM: 70–93 fibers/9 muscles at 4.7 mM K+ and 39–80 fibers/6 muscles for all other conditions. *, Mean tetanic force or resting EM of HyperKPP muscle was significantly different from the mean values of wild-type muscle, ANOVA, and LSD, P < 0.05.
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fig8: Ouabain caused greater loss of tetanic force and membrane depolarization in HyperKPP, EDL, and soleus than in diaphragm. (A–C) All muscles were allowed a 30-min equilibrium at 4.7 mM K+ before any measurements or changes in [K+]e or ouabain. For force measurements, muscles were exposed 20 min to ouabain while being exposed to 4.7 mM K+ before [K+]e was increased to 9 mM, still in the presence of ouabain as indicated in the figures. A similar approach was used for resting EM with half the muscles; for the other half, muscles were exposed to ouabain only after [K+]e had been raised to 9 mM K+. The resting EM at 9 mM and 1 µM ouabain was not different between the two approaches, so the data were pooled. Error bars represent SEM; force of five muscles; resting EM: 70–93 fibers/9 muscles at 4.7 mM K+ and 39–80 fibers/6 muscles for all other conditions. *, Mean tetanic force or resting EM of HyperKPP muscle was significantly different from the mean values of wild-type muscle, ANOVA, and LSD, P < 0.05.

Mentions: Next, we assessed how inhibiting NKA activity with ouabain affected tetanic force and resting EM. We first used ouabain at a concentration of 1 µM to reduce NKAα2 activity by 92% and that of NKAα1 by 6% according to the ouabain Ki values reported by Chibalin et al. (2012) that were measured from changes in rat diaphragm resting EM after exposure to various ouabain concentrations. At 4.7 mM K+, 1 µM ouabain reduced mean tetanic force of wild-type soleus by 7%, whereas resting EM depolarized by 8 mV (Fig. 8 A). The decrease in tetanic force for HyperKPP soleus was much larger at 42% despite a similar depolarization of 7 mV. Ouabain also caused a greater decrease in force at 9 mM K+ in HyperKPP soleus, even though the ouabain-induced membrane depolarization was 7 mV in wild type and 9 mV in HyperKPP. The apparent greater ouabain effect on HyperKPP soleus force despite a similar extent of depolarizations was because in the absence of ouabain, resting EM at 4.7 mM K+ was −75 and −60 mV in wild-type and HyperKPP soleus, respectively. As per the tetanic force–resting EM curve (Fig. 5 A), small 7–9-mV depolarization is expected to have small effects on wild-type force, whereas in HyperKPP soleus, the effects were greater because the starting resting EM was in the steepest portion of the curve. The ouabain and K+ effects in EDL (Fig. 8 B) resembled those of soleus.


Understanding the physiology of the asymptomatic diaphragm of the M1592V hyperkalemic periodic paralysis mouse.

Ammar T, Lin W, Higgins A, Hayward LJ, Renaud JM - J. Gen. Physiol. (2015)

Ouabain caused greater loss of tetanic force and membrane depolarization in HyperKPP, EDL, and soleus than in diaphragm. (A–C) All muscles were allowed a 30-min equilibrium at 4.7 mM K+ before any measurements or changes in [K+]e or ouabain. For force measurements, muscles were exposed 20 min to ouabain while being exposed to 4.7 mM K+ before [K+]e was increased to 9 mM, still in the presence of ouabain as indicated in the figures. A similar approach was used for resting EM with half the muscles; for the other half, muscles were exposed to ouabain only after [K+]e had been raised to 9 mM K+. The resting EM at 9 mM and 1 µM ouabain was not different between the two approaches, so the data were pooled. Error bars represent SEM; force of five muscles; resting EM: 70–93 fibers/9 muscles at 4.7 mM K+ and 39–80 fibers/6 muscles for all other conditions. *, Mean tetanic force or resting EM of HyperKPP muscle was significantly different from the mean values of wild-type muscle, ANOVA, and LSD, P < 0.05.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4664826&req=5

fig8: Ouabain caused greater loss of tetanic force and membrane depolarization in HyperKPP, EDL, and soleus than in diaphragm. (A–C) All muscles were allowed a 30-min equilibrium at 4.7 mM K+ before any measurements or changes in [K+]e or ouabain. For force measurements, muscles were exposed 20 min to ouabain while being exposed to 4.7 mM K+ before [K+]e was increased to 9 mM, still in the presence of ouabain as indicated in the figures. A similar approach was used for resting EM with half the muscles; for the other half, muscles were exposed to ouabain only after [K+]e had been raised to 9 mM K+. The resting EM at 9 mM and 1 µM ouabain was not different between the two approaches, so the data were pooled. Error bars represent SEM; force of five muscles; resting EM: 70–93 fibers/9 muscles at 4.7 mM K+ and 39–80 fibers/6 muscles for all other conditions. *, Mean tetanic force or resting EM of HyperKPP muscle was significantly different from the mean values of wild-type muscle, ANOVA, and LSD, P < 0.05.
Mentions: Next, we assessed how inhibiting NKA activity with ouabain affected tetanic force and resting EM. We first used ouabain at a concentration of 1 µM to reduce NKAα2 activity by 92% and that of NKAα1 by 6% according to the ouabain Ki values reported by Chibalin et al. (2012) that were measured from changes in rat diaphragm resting EM after exposure to various ouabain concentrations. At 4.7 mM K+, 1 µM ouabain reduced mean tetanic force of wild-type soleus by 7%, whereas resting EM depolarized by 8 mV (Fig. 8 A). The decrease in tetanic force for HyperKPP soleus was much larger at 42% despite a similar depolarization of 7 mV. Ouabain also caused a greater decrease in force at 9 mM K+ in HyperKPP soleus, even though the ouabain-induced membrane depolarization was 7 mV in wild type and 9 mV in HyperKPP. The apparent greater ouabain effect on HyperKPP soleus force despite a similar extent of depolarizations was because in the absence of ouabain, resting EM at 4.7 mM K+ was −75 and −60 mV in wild-type and HyperKPP soleus, respectively. As per the tetanic force–resting EM curve (Fig. 5 A), small 7–9-mV depolarization is expected to have small effects on wild-type force, whereas in HyperKPP soleus, the effects were greater because the starting resting EM was in the steepest portion of the curve. The ouabain and K+ effects in EDL (Fig. 8 B) resembled those of soleus.

Bottom Line: The improved resting membrane potential (EM) results from significantly increased Na(+) K(+) pump electrogenic activity, and not from an increased protein content.One suggested mechanism for the greater action potential amplitude is lower intracellular Na(+) concentration because of greater Na(+) K(+) pump activity, allowing better Na(+) current during the action potential depolarization phase.Finally, HyperKPP diaphragm had a greater capacity to generate force at depolarized EM compared with wild-type diaphragm.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada.

No MeSH data available.


Related in: MedlinePlus