Limits...
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 fibers were more depolarized than wild-type fibers. Each muscle was tested at one or two elevated [K+]e. Resting EM was measured in several fibers in each muscles. (A–C) An average resting EM was calculated for each muscle, and from the muscle averages a final mean was calculated. Error bars represent the SEM of 209–278 fibers/19 muscles at 4.7 mM K+ and 65–107 fibers/5–6 muscles at other [K+]e. Numbers below the resting EM at 4.7 mM K+ indicate the slope and SEM of the membrane depolarization (in mV/[K+]e decade) using the mean resting EM versus log([K+]e); calculations were performed using the LINEST function of Excel 2013 (correlation coefficients of the analyses ranged from 0.973 to 0.999). *, mean resting EM of HyperKPP muscle was significantly different from the mean value of wild-type muscle; ANOVA and LSD; P < 0.05.
© Copyright Policy - openaccess
Related In: Results  -  Collection

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

fig3: HyperKPP soleus and EDL but not diaphragm fibers were more depolarized than wild-type fibers. Each muscle was tested at one or two elevated [K+]e. Resting EM was measured in several fibers in each muscles. (A–C) An average resting EM was calculated for each muscle, and from the muscle averages a final mean was calculated. Error bars represent the SEM of 209–278 fibers/19 muscles at 4.7 mM K+ and 65–107 fibers/5–6 muscles at other [K+]e. Numbers below the resting EM at 4.7 mM K+ indicate the slope and SEM of the membrane depolarization (in mV/[K+]e decade) using the mean resting EM versus log([K+]e); calculations were performed using the LINEST function of Excel 2013 (correlation coefficients of the analyses ranged from 0.973 to 0.999). *, mean resting EM of HyperKPP muscle was significantly different from the mean value of wild-type muscle; ANOVA and LSD; P < 0.05.

Mentions: HyperKPP muscle fibers are known to have less negative resting EM than normal fibers (Lehmann-Horn et al., 1983, 1987; Ricker et al., 1989; Clausen et al., 2011). Furthermore, the K+-induced force depression is caused by a depolarization of the cell membrane, which then causes an inactivation of NaV1.4 channels (Renaud and Light, 1992; Cairns et al., 1997; Yensen et al., 2002). To better understand the importance of the membrane depolarization in the lower force generated by HyperKPP EDL and soleus or the conservation of force for the diaphragm, we measured resting EM in 10–15 fibers chosen at random from the muscle surface at different [K+]e (note here that action potentials were not measured to determine if a fiber was excitable or not). At 4.7 mM K+, mean resting EM was 15 mV lower in HyperKPP than in wild-type soleus, a difference that became smaller as [K+]e was increased because the K+-induced membrane depolarization per [K+]e decade was smaller in HyperKPP soleus (Fig. 3 A). For EDL, the difference in resting EM between wild-type and HyperKPP was smaller, being 5–9 mV among the different [K+]e as the slopes of the membrane depolarization were not different between wild type and HyperKPP (Fig. 3 B). The smallest difference in resting EM between wild type and HyperKPP was with the diaphragm, being only 2–4 mV and nonsignificant at all [K+]e (Fig. 3 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)

HyperKPP soleus and EDL but not diaphragm fibers were more depolarized than wild-type fibers. Each muscle was tested at one or two elevated [K+]e. Resting EM was measured in several fibers in each muscles. (A–C) An average resting EM was calculated for each muscle, and from the muscle averages a final mean was calculated. Error bars represent the SEM of 209–278 fibers/19 muscles at 4.7 mM K+ and 65–107 fibers/5–6 muscles at other [K+]e. Numbers below the resting EM at 4.7 mM K+ indicate the slope and SEM of the membrane depolarization (in mV/[K+]e decade) using the mean resting EM versus log([K+]e); calculations were performed using the LINEST function of Excel 2013 (correlation coefficients of the analyses ranged from 0.973 to 0.999). *, mean resting EM of HyperKPP muscle was significantly different from the mean value 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

fig3: HyperKPP soleus and EDL but not diaphragm fibers were more depolarized than wild-type fibers. Each muscle was tested at one or two elevated [K+]e. Resting EM was measured in several fibers in each muscles. (A–C) An average resting EM was calculated for each muscle, and from the muscle averages a final mean was calculated. Error bars represent the SEM of 209–278 fibers/19 muscles at 4.7 mM K+ and 65–107 fibers/5–6 muscles at other [K+]e. Numbers below the resting EM at 4.7 mM K+ indicate the slope and SEM of the membrane depolarization (in mV/[K+]e decade) using the mean resting EM versus log([K+]e); calculations were performed using the LINEST function of Excel 2013 (correlation coefficients of the analyses ranged from 0.973 to 0.999). *, mean resting EM of HyperKPP muscle was significantly different from the mean value of wild-type muscle; ANOVA and LSD; P < 0.05.
Mentions: HyperKPP muscle fibers are known to have less negative resting EM than normal fibers (Lehmann-Horn et al., 1983, 1987; Ricker et al., 1989; Clausen et al., 2011). Furthermore, the K+-induced force depression is caused by a depolarization of the cell membrane, which then causes an inactivation of NaV1.4 channels (Renaud and Light, 1992; Cairns et al., 1997; Yensen et al., 2002). To better understand the importance of the membrane depolarization in the lower force generated by HyperKPP EDL and soleus or the conservation of force for the diaphragm, we measured resting EM in 10–15 fibers chosen at random from the muscle surface at different [K+]e (note here that action potentials were not measured to determine if a fiber was excitable or not). At 4.7 mM K+, mean resting EM was 15 mV lower in HyperKPP than in wild-type soleus, a difference that became smaller as [K+]e was increased because the K+-induced membrane depolarization per [K+]e decade was smaller in HyperKPP soleus (Fig. 3 A). For EDL, the difference in resting EM between wild-type and HyperKPP was smaller, being 5–9 mV among the different [K+]e as the slopes of the membrane depolarization were not different between wild type and HyperKPP (Fig. 3 B). The smallest difference in resting EM between wild type and HyperKPP was with the diaphragm, being only 2–4 mV and nonsignificant at all [K+]e (Fig. 3 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