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Verapamil and NAC reduce the excess and damaging increase in myoplasmic calcium concentration during fatigue
Author(s) -
Selvin David,
Renaud JeanMarc
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1051.1
Subject(s) - verapamil , medicine , chemistry , endocrinology , calcium , resting potential , channel blocker , contractility , l type calcium channel , calcium channel , membrane potential , biophysics , biology , biochemistry
Muscles that lack K ATP channel activity generate much greater resting [Ca 2+ ]i and force than normal muscles. The large increase in resting force in K ATP channel deficient muscles is completely abolished with 1 μM verapamil, a L‐type Ca 2+ channel blocker, which suggests that the increase in resting force was due to a Ca 2+ influx through L‐type Ca 2+ channel. However, we recently found that NAC, a ROS scavenger, also reduces resting force. The objective of this study was to test the hypothesis that “the excess increases in resting [Ca 2+ ]i during fatigue in K ATP channel deficient muscles starts with an excess Ca 2+ influx through L‐type Ca 2+ channels, followed by excess ROS production that somehow causes a further increase in resting [Ca 2+ ]i”. At 1 μm, verapamil had no effect on tetanic and resting Ca 2+ before fatigue, but significantly reduced resting [Ca 2+ ]i in K ATP channel deficient fibers. At 1 mM, NAC did not affect contractility and reduced the increase in resting [Ca 2+ ]i in K ATP channel deficient fibers. It is therefore suggested that the excess increased in resting [Ca 2+ ]i during fatigue in K ATP channel deficient FDB fibers is not completely due to an influx through L‐type Ca 2+ channels as it may involve excess ROS production acting on proteins that regulate [Ca 2+ ]i (e.g., the Ca 2+ ATPase).