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Hyperpolarized shifts in the voltage dependence of fast inactivation of Na v 1.4 and Na v 1.5 in a rat model of critical illness myopathy
Author(s) -
Filatov Gregory N.,
Rich Mark M.
Publication year - 2004
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2004.062349
Subject(s) - sodium channel , skeletal muscle , denervation , myopathy , chemistry , in vivo , medicine , endocrinology , nav1 , biophysics , biology , sodium , genetics , organic chemistry
Critical illness myopathy is a disorder in which skeletal muscle becomes electrically inexcitable. We previously demonstrated that a shift in the voltage dependence of fast inactivation of sodium currents contributes to inexcitability of affected fibres in an animal model of critical illness myopathy in which denervated rat skeletal muscle is treated with corticosteroids (steroid‐denervated; SD). In the current study we examined whether expression of Na v 1.5 contributes to the altered voltage dependence of sodium channel inactivation in SD muscle. We used TTX and μ‐conotoxin GIIIB to selectively block Na v 1.4 in SD muscle and found that the level of Na v 1.5 did not correlate closely with the shift in fast inactivation. Surprisingly, we found that the voltage dependence of inactivation of Na v 1.4 was similar to that of Na v 1.5 in skeletal muscle in vivo . In severely affected fibres, inactivation of both Na v 1.4 and Na v 1.5 was shifted towards hyperpolarized potentials. We examined the role of denervation and steroid treatment in the shift of the voltage dependence of inactivation and found that both denervation and steroid treatment contribute to the shift in inactivation. Our results suggest that modulation of the voltage dependence of inactivation of both Na v 1.4 and Na v 1.5 in vivo contributes to loss of electrical excitability in SD muscle.