scholarly journals Na+ channel mis-expression accelerates K+ channel development in embryonic Xenopus laevis skeletal muscle.

1994 ◽  
Vol 480 (3) ◽  
pp. 405-410 ◽  
Author(s):  
P Linsdell ◽  
W J Moody
2007 ◽  
Vol 130 (1) ◽  
pp. 11-20 ◽  
Author(s):  
Arie F. Struyk ◽  
Stephen C. Cannon

The heritable muscle disorder hypokalemic periodic paralysis (HypoPP) is characterized by attacks of flaccid weakness, brought on by sustained sarcolemmal depolarization. HypoPP is genetically linked to missense mutations at charged residues in the S4 voltage-sensing segments of either CaV1.1 (the skeletal muscle L-type Ca2+ channel) or NaV1.4 (the skeletal muscle voltage-gated Na+ channel). Although these mutations alter the gating of both channels, these functional defects have proven insufficient to explain the sarcolemmal depolarization in affected muscle. Recent insight into the topology of the S4 voltage-sensing domain has aroused interest in an alternative pathomechanism, wherein HypoPP mutations might generate an aberrant ionic leak conductance by unblocking the putative aqueous crevice (“gating-pore”) in which the S4 segment resides. We tested the rat isoform of NaV1.4 harboring the HypoPP mutation R663H (human R669H ortholog) at the outermost arginine of S4 in domain II for a gating-pore conductance. We found that the mutation R663H permits transmembrane permeation of protons, but not larger cations, similar to the conductance displayed by histidine substitution at Shaker K+ channel S4 sites. These results are consistent with the notion that the outermost charged residue in the DIIS4 segment is simultaneously accessible to the cytoplasmic and extracellular spaces when the voltage sensor is positioned inwardly. The predicted magnitude of this proton leak in mature skeletal muscle is small relative to the resting K+ and Cl− conductances, and is thus not likely to fully account for the aberrant sarcolemmal depolarization underlying the paralytic attacks. Rather, it is possible that a sustained proton leak may contribute to instability of VREST indirectly, for instance, by interfering with intracellular pH homeostasis.


2021 ◽  
Vol 22 (9) ◽  
pp. 4407
Author(s):  
Dana Adler ◽  
Zehavit Shapira ◽  
Shimon Weiss ◽  
Asher Shainberg ◽  
Abram Katz

Weak electromagnetic fields (WEF) alter Ca2+ handling in skeletal muscle myotubes. Owing to the involvement of Ca2+ in muscle development, we investigated whether WEF affects fusion of myoblasts in culture. Rat primary myoblast cultures were exposed to WEF (1.75 µT, 16 Hz) for up to six days. Under control conditions, cell fusion and creatine kinase (CK) activity increased in parallel and peaked at 4–6 days. WEF enhanced the extent of fusion after one and two days (by ~40%) vs. control, but not thereafter. Exposure to WEF also enhanced CK activity after two days (almost four-fold), but not afterwards. Incorporation of 3H-thymidine into DNA was enhanced by one-day exposure to WEF (~40%), indicating increased cell replication. Using the potentiometric fluorescent dye di-8-ANEPPS, we found that exposure of cells to 150 mM KCl resulted in depolarization of the cell membrane. However, prior exposure of cells to WEF for one day followed by addition of KCl resulted in hyperpolarization of the cell membrane. Acute exposure of cells to WEF also resulted in hyperpolarization of the cell membrane. Twenty-four hour incubation of myoblasts with gambogic acid, an inhibitor of the inward rectifying K+ channel 2.1 (Kir2.1), did not affect cell fusion, WEF-mediated acceleration of fusion or hyperpolarization. These data demonstrate that WEF accelerates fusion of myoblasts, resulting in myotube formation. The WEF effect is associated with hyperpolarization but WEF does not appear to mediate its effects on fusion by activating Kir2.1 channels.


2006 ◽  
Vol 20 (9) ◽  
pp. 1531-1533 ◽  
Author(s):  
Xun Wang ◽  
Gregory H. Hockerman ◽  
Henry W. Green ◽  
Charles F. Babbs ◽  
Sulma I. Mohammad ◽  
...  

Biochemistry ◽  
1998 ◽  
Vol 37 (13) ◽  
pp. 4407-4419 ◽  
Author(s):  
Nancy S. Chang ◽  
Robert J. French ◽  
Gregory M. Lipkind ◽  
Harry A. Fozzard ◽  
Samuel Dudley
Keyword(s):  

PLoS ONE ◽  
2014 ◽  
Vol 9 (6) ◽  
pp. e98863 ◽  
Author(s):  
Zahra Nourian ◽  
Min Li ◽  
M. Dennis Leo ◽  
Jonathan H. Jaggar ◽  
Andrew P. Braun ◽  
...  

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