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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

ORM-10103 caused small decreases in tetanic force in the wild-type diaphragm and in the HyperKPP EDL and diaphragm, but not in wild type EDL. (A–D) Muscles were first exposed to 3 µM ORM-10103, an NCX inhibitor, while being exposed to 4.7 mM K+. The increase in [K+]e was to 12.5 mM for all muscles, except for the HyperKPP EDL, for which the increase was to 11 mM K+, as this muscle was more sensitive to the K+-induced force depression. Error bars represent the SEM of 5 muscles. *, mean tetanic force of ORM-10103–exposed muscles was significantly less than the mean value of control; ANOVA and LSD; P < 0.05.
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fig11: ORM-10103 caused small decreases in tetanic force in the wild-type diaphragm and in the HyperKPP EDL and diaphragm, but not in wild type EDL. (A–D) Muscles were first exposed to 3 µM ORM-10103, an NCX inhibitor, while being exposed to 4.7 mM K+. The increase in [K+]e was to 12.5 mM for all muscles, except for the HyperKPP EDL, for which the increase was to 11 mM K+, as this muscle was more sensitive to the K+-induced force depression. Error bars represent the SEM of 5 muscles. *, mean tetanic force of ORM-10103–exposed muscles was significantly less than the mean value of control; ANOVA and LSD; P < 0.05.

Mentions: The effects of ORM-10103 were first tested in wild-type EDL, as this muscle is the least dependent on extracellular Ca2+ (Viirès et al., 1988) and for which there is no evidence for a role of NCX during contractions (Blaustein and Lederer, 1999). As expected, ORM-10103 had no effect on tetanic force of that muscle at 4.7 and 12.5 mM K+ (Fig. 11 A). ORM-10103 had no effect on HyperKPP EDL while exposed to 4.7 mM K+, but the force loss at 11 mM K+ was greater in the presence of ORM-10103 (Fig. 11 B). Similarly, the decrease in tetanic force in the wild-type and HyperKPP diaphragm at 12.5 mM K+ was greater in the presence than in the absence of ORM-10103 (Fig. 11, C and D). However, the difference in force in the absence and presence of ORM-10103 at 12.5 mM K+ was the same for the wild-type and HyperKPP diaphragm, suggesting that an increased NCX activity in the reverse mode is not a mechanism that can explain the greater force in the HyperKPP diaphragm at depolarized resting EM (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)

ORM-10103 caused small decreases in tetanic force in the wild-type diaphragm and in the HyperKPP EDL and diaphragm, but not in wild type EDL. (A–D) Muscles were first exposed to 3 µM ORM-10103, an NCX inhibitor, while being exposed to 4.7 mM K+. The increase in [K+]e was to 12.5 mM for all muscles, except for the HyperKPP EDL, for which the increase was to 11 mM K+, as this muscle was more sensitive to the K+-induced force depression. Error bars represent the SEM of 5 muscles. *, mean tetanic force of ORM-10103–exposed muscles was significantly less than the mean value of control; 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

fig11: ORM-10103 caused small decreases in tetanic force in the wild-type diaphragm and in the HyperKPP EDL and diaphragm, but not in wild type EDL. (A–D) Muscles were first exposed to 3 µM ORM-10103, an NCX inhibitor, while being exposed to 4.7 mM K+. The increase in [K+]e was to 12.5 mM for all muscles, except for the HyperKPP EDL, for which the increase was to 11 mM K+, as this muscle was more sensitive to the K+-induced force depression. Error bars represent the SEM of 5 muscles. *, mean tetanic force of ORM-10103–exposed muscles was significantly less than the mean value of control; ANOVA and LSD; P < 0.05.
Mentions: The effects of ORM-10103 were first tested in wild-type EDL, as this muscle is the least dependent on extracellular Ca2+ (Viirès et al., 1988) and for which there is no evidence for a role of NCX during contractions (Blaustein and Lederer, 1999). As expected, ORM-10103 had no effect on tetanic force of that muscle at 4.7 and 12.5 mM K+ (Fig. 11 A). ORM-10103 had no effect on HyperKPP EDL while exposed to 4.7 mM K+, but the force loss at 11 mM K+ was greater in the presence of ORM-10103 (Fig. 11 B). Similarly, the decrease in tetanic force in the wild-type and HyperKPP diaphragm at 12.5 mM K+ was greater in the presence than in the absence of ORM-10103 (Fig. 11, C and D). However, the difference in force in the absence and presence of ORM-10103 at 12.5 mM K+ was the same for the wild-type and HyperKPP diaphragm, suggesting that an increased NCX activity in the reverse mode is not a mechanism that can explain the greater force in the HyperKPP diaphragm at depolarized resting EM (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