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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

Effect of 10 µM ouabain at 9 mM K+ and 100 µM ouabain at 4.7 mM K+. Effects of 10 µM ouabain added as [K+]e was increased to 9 mM on (A) tetanic force and (B) resting EM of diaphragm. Effects of 100 µM ouabain at 4.7 mM K+ on (C) tetanic force in diaphragm and (D) resting EM of soleus (S), EDL (E), and diaphragm (D). Error bars represent the SEM of 5 muscles (A and B) and 86–177 fibers/5 muscles (C and D). *, 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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fig9: Effect of 10 µM ouabain at 9 mM K+ and 100 µM ouabain at 4.7 mM K+. Effects of 10 µM ouabain added as [K+]e was increased to 9 mM on (A) tetanic force and (B) resting EM of diaphragm. Effects of 100 µM ouabain at 4.7 mM K+ on (C) tetanic force in diaphragm and (D) resting EM of soleus (S), EDL (E), and diaphragm (D). Error bars represent the SEM of 5 muscles (A and B) and 86–177 fibers/5 muscles (C and D). *, 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: The situation was very different with the diaphragm (Fig. 8 C). First, the decrease in force upon exposure to 1 µM ouabain at 4.7 mM K+ was not different between the wild-type and HyperKPP diaphragm because resting EM in the presence of ouabain did not decrease below −72 mV for wild type and −63 mV for HyperKPP; i.e., resting EM remained in a range for which there is little effect on tetanic force (Fig. 5 C). Second, although the decrease in tetanic force in the wild-type diaphragm upon raising [K+]e to 9 mM at 1 µM ouabain was similar to that of wild-type soleus and EDL, the decrease in the HyperKPP diaphragm was only 42% compared with 89–91% in soleus and EDL. For a complete loss of force in the HyperKPP diaphragm at 9 mM K+, the HyperKPP diaphragm had to be exposed to 10 µM ouabain (Fig. 9 A), which fully inhibits NKAα2 and NKAα1 by 37% (Chibalin et al., 2012). The large decrease in force in that condition was related to a membrane depolarization to −50 mV (Fig. 9 B), a EM at which tetanic force is expected to be zero in the HyperKPP diaphragm (Fig. 5 C).


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)

Effect of 10 µM ouabain at 9 mM K+ and 100 µM ouabain at 4.7 mM K+. Effects of 10 µM ouabain added as [K+]e was increased to 9 mM on (A) tetanic force and (B) resting EM of diaphragm. Effects of 100 µM ouabain at 4.7 mM K+ on (C) tetanic force in diaphragm and (D) resting EM of soleus (S), EDL (E), and diaphragm (D). Error bars represent the SEM of 5 muscles (A and B) and 86–177 fibers/5 muscles (C and D). *, 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

fig9: Effect of 10 µM ouabain at 9 mM K+ and 100 µM ouabain at 4.7 mM K+. Effects of 10 µM ouabain added as [K+]e was increased to 9 mM on (A) tetanic force and (B) resting EM of diaphragm. Effects of 100 µM ouabain at 4.7 mM K+ on (C) tetanic force in diaphragm and (D) resting EM of soleus (S), EDL (E), and diaphragm (D). Error bars represent the SEM of 5 muscles (A and B) and 86–177 fibers/5 muscles (C and D). *, 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: The situation was very different with the diaphragm (Fig. 8 C). First, the decrease in force upon exposure to 1 µM ouabain at 4.7 mM K+ was not different between the wild-type and HyperKPP diaphragm because resting EM in the presence of ouabain did not decrease below −72 mV for wild type and −63 mV for HyperKPP; i.e., resting EM remained in a range for which there is little effect on tetanic force (Fig. 5 C). Second, although the decrease in tetanic force in the wild-type diaphragm upon raising [K+]e to 9 mM at 1 µM ouabain was similar to that of wild-type soleus and EDL, the decrease in the HyperKPP diaphragm was only 42% compared with 89–91% in soleus and EDL. For a complete loss of force in the HyperKPP diaphragm at 9 mM K+, the HyperKPP diaphragm had to be exposed to 10 µM ouabain (Fig. 9 A), which fully inhibits NKAα2 and NKAα1 by 37% (Chibalin et al., 2012). The large decrease in force in that condition was related to a membrane depolarization to −50 mV (Fig. 9 B), a EM at which tetanic force is expected to be zero in the HyperKPP diaphragm (Fig. 5 C).

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