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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

HyperKPP soleus and EDL but not diaphragm generated less tetanic force than wild-type muscles. (A–C) Tetanic force was elicited with a 200-msec train of 0.3 msec, 10-V square pulses at 140 Hz for the soleus and 200 Hz for the EDL and diaphragm. Data were acquired immediately after adjusting the length for maximum force at the beginning of an experiment. The tetanic forces from every experiment including those for EM measurements were used to calculate mean tetanic force. Error bars represent the SEM of 24 solei, 34 EDL, and 44 diaphragms. *, mean tetanic force of HyperKPP muscles was significantly different from that of wild type; ANOVA and LSD; P < 0.05.
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fig1: HyperKPP soleus and EDL but not diaphragm generated less tetanic force than wild-type muscles. (A–C) Tetanic force was elicited with a 200-msec train of 0.3 msec, 10-V square pulses at 140 Hz for the soleus and 200 Hz for the EDL and diaphragm. Data were acquired immediately after adjusting the length for maximum force at the beginning of an experiment. The tetanic forces from every experiment including those for EM measurements were used to calculate mean tetanic force. Error bars represent the SEM of 24 solei, 34 EDL, and 44 diaphragms. *, mean tetanic force of HyperKPP muscles was significantly different from that of wild type; ANOVA and LSD; P < 0.05.

Mentions: As mentioned in the Introduction, the K+-induced force depression starts with a membrane depolarization. So, we first analyzed the K+ effects on tetanic force and resting EM to construct tetanic force–resting EM relationships to document how much of the force losses in HyperKPP muscles compared with wild type are related to membrane depolarization. At 4.7 mM K+ (control), mean tetanic forces using the data from all tested HyperKPP soleus and EDL in this study were significantly lower than their wild-type counterparts. Wild-type and HyperKPP soleus, respectively, generated on average a tetanic force of 19.3 and 12.7 N/cm2; i.e., mean tetanic force of HyperKPP soleus was 66% of the wild-type force (Fig. 1 A). Wild-type and HyperKPP EDL, respectively, generated 29.8 and 22.7 N/cm2 for a HyperKPP force being 76% of wild type (Fig. 1 B). For the diaphragm, however, there was no significant difference between wild type and HyperKPP (Fig. 1 C). The relative decreases in mean tetanic force of HyperKPP soleus and EDL at 9–11 mM K+ were significantly greater in HyperKPP than in wild-type EDL and soleus (Fig. 2, A and B) but not in the diaphragm, as there was no difference between wild-type and HyperKPP (Fig. 2 C). Thus, HyperKPP diaphragms do not have a greater sensitivity to the K+-induced force depression as observed with EDL and 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)

HyperKPP soleus and EDL but not diaphragm generated less tetanic force than wild-type muscles. (A–C) Tetanic force was elicited with a 200-msec train of 0.3 msec, 10-V square pulses at 140 Hz for the soleus and 200 Hz for the EDL and diaphragm. Data were acquired immediately after adjusting the length for maximum force at the beginning of an experiment. The tetanic forces from every experiment including those for EM measurements were used to calculate mean tetanic force. Error bars represent the SEM of 24 solei, 34 EDL, and 44 diaphragms. *, mean tetanic force of HyperKPP muscles was significantly different from that of wild type; 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

fig1: HyperKPP soleus and EDL but not diaphragm generated less tetanic force than wild-type muscles. (A–C) Tetanic force was elicited with a 200-msec train of 0.3 msec, 10-V square pulses at 140 Hz for the soleus and 200 Hz for the EDL and diaphragm. Data were acquired immediately after adjusting the length for maximum force at the beginning of an experiment. The tetanic forces from every experiment including those for EM measurements were used to calculate mean tetanic force. Error bars represent the SEM of 24 solei, 34 EDL, and 44 diaphragms. *, mean tetanic force of HyperKPP muscles was significantly different from that of wild type; ANOVA and LSD; P < 0.05.
Mentions: As mentioned in the Introduction, the K+-induced force depression starts with a membrane depolarization. So, we first analyzed the K+ effects on tetanic force and resting EM to construct tetanic force–resting EM relationships to document how much of the force losses in HyperKPP muscles compared with wild type are related to membrane depolarization. At 4.7 mM K+ (control), mean tetanic forces using the data from all tested HyperKPP soleus and EDL in this study were significantly lower than their wild-type counterparts. Wild-type and HyperKPP soleus, respectively, generated on average a tetanic force of 19.3 and 12.7 N/cm2; i.e., mean tetanic force of HyperKPP soleus was 66% of the wild-type force (Fig. 1 A). Wild-type and HyperKPP EDL, respectively, generated 29.8 and 22.7 N/cm2 for a HyperKPP force being 76% of wild type (Fig. 1 B). For the diaphragm, however, there was no significant difference between wild type and HyperKPP (Fig. 1 C). The relative decreases in mean tetanic force of HyperKPP soleus and EDL at 9–11 mM K+ were significantly greater in HyperKPP than in wild-type EDL and soleus (Fig. 2, A and B) but not in the diaphragm, as there was no difference between wild-type and HyperKPP (Fig. 2 C). Thus, HyperKPP diaphragms do not have a greater sensitivity to the K+-induced force depression as observed with EDL and 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