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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

NKAα1 protein content was significantly higher in HyperKPP than in wild-type EDL, whereas there was no difference for the soleus, diaphragm, and FDB muscles. (A) For each muscle, NKAα1 contents were calculated as a ratio of the content in wild-type muscle. (B) For each of wild-type and HyperKPP, NKAα1 contents were calculated as a ratio of the EDL content. Error bars represent the SEM of five muscles. §, mean NKAα1 content significantly different from mean content in EDL; *, mean NKAα1 content was significantly different from wild-type content; ANOVA and LSD; P < 0.05.
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fig6: NKAα1 protein content was significantly higher in HyperKPP than in wild-type EDL, whereas there was no difference for the soleus, diaphragm, and FDB muscles. (A) For each muscle, NKAα1 contents were calculated as a ratio of the content in wild-type muscle. (B) For each of wild-type and HyperKPP, NKAα1 contents were calculated as a ratio of the EDL content. Error bars represent the SEM of five muscles. §, mean NKAα1 content significantly different from mean content in EDL; *, mean NKAα1 content was significantly different from wild-type content; ANOVA and LSD; P < 0.05.

Mentions: For the measurements of NKAα1 and NKAα2 protein content, we included the FDB because it is also an asymptomatic muscle, but contrary to the diaphragm, it has a very low TTX-sensitive Na+ influx even though its NaV1.4 channel protein content is comparable to that of soleus (Lucas et al., 2014). Here, we first determined whether the NKA protein content is greater in HyperKPP than in the wild-type diaphragm, as has been reported for HyperKPP EDL (Clausen et al., 2011). HyperKPP EDL was the only muscle with significantly greater NKAα1 protein content than in the wild-type counterpart (Fig. 6 A). Next, we determined how the large increase in NKAα1 protein content in HyperKPP EDL affected the relative differences between muscles in wild type and HyperKPP. Although wild-type EDL had two to three times less NKAα1 content compared with soleus, diaphragm, and FDB, the NKAα1 content in HyperKPP EDL was no longer different from the other three muscles (Fig. 6 B). The situation was the same for the NKAα2 protein content. That is, HyperKPP EDL had a greater NKAα2 content than in wild type (Fig. 7 A). As a consequence of the increase, the wild-type diaphragm had similar NKAα2 protein content to wild-type EDL, whereas for HyperKPP NKAα2, the content was less in the diaphragm than in EDL (Fig. 7 B). It was also noted that the 83% higher content in HyperKPP than in wild-type EDL as well as the 21% higher content in HyperKPP soleus were similar to the values reported from ouabain-binding studies (Clausen et al., 2011).


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)

NKAα1 protein content was significantly higher in HyperKPP than in wild-type EDL, whereas there was no difference for the soleus, diaphragm, and FDB muscles. (A) For each muscle, NKAα1 contents were calculated as a ratio of the content in wild-type muscle. (B) For each of wild-type and HyperKPP, NKAα1 contents were calculated as a ratio of the EDL content. Error bars represent the SEM of five muscles. §, mean NKAα1 content significantly different from mean content in EDL; *, mean NKAα1 content was significantly different from wild-type content; 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

fig6: NKAα1 protein content was significantly higher in HyperKPP than in wild-type EDL, whereas there was no difference for the soleus, diaphragm, and FDB muscles. (A) For each muscle, NKAα1 contents were calculated as a ratio of the content in wild-type muscle. (B) For each of wild-type and HyperKPP, NKAα1 contents were calculated as a ratio of the EDL content. Error bars represent the SEM of five muscles. §, mean NKAα1 content significantly different from mean content in EDL; *, mean NKAα1 content was significantly different from wild-type content; ANOVA and LSD; P < 0.05.
Mentions: For the measurements of NKAα1 and NKAα2 protein content, we included the FDB because it is also an asymptomatic muscle, but contrary to the diaphragm, it has a very low TTX-sensitive Na+ influx even though its NaV1.4 channel protein content is comparable to that of soleus (Lucas et al., 2014). Here, we first determined whether the NKA protein content is greater in HyperKPP than in the wild-type diaphragm, as has been reported for HyperKPP EDL (Clausen et al., 2011). HyperKPP EDL was the only muscle with significantly greater NKAα1 protein content than in the wild-type counterpart (Fig. 6 A). Next, we determined how the large increase in NKAα1 protein content in HyperKPP EDL affected the relative differences between muscles in wild type and HyperKPP. Although wild-type EDL had two to three times less NKAα1 content compared with soleus, diaphragm, and FDB, the NKAα1 content in HyperKPP EDL was no longer different from the other three muscles (Fig. 6 B). The situation was the same for the NKAα2 protein content. That is, HyperKPP EDL had a greater NKAα2 content than in wild type (Fig. 7 A). As a consequence of the increase, the wild-type diaphragm had similar NKAα2 protein content to wild-type EDL, whereas for HyperKPP NKAα2, the content was less in the diaphragm than in EDL (Fig. 7 B). It was also noted that the 83% higher content in HyperKPP than in wild-type EDL as well as the 21% higher content in HyperKPP soleus were similar to the values reported from ouabain-binding studies (Clausen et al., 2011).

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