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- Title
Hyperpolarized shifts in the voltage dependence of fast inactivation of Na<sub>v</sub>1.4 and Na<sub>v</sub>1.5 in a rat model of critical illness myopathy.
- Authors
Filatov, Gregory N.; Rich, Mark M.
- Abstract
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 Nav 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 Nav 1.4 in SD muscle and found that the level of Nav 1.5 did not correlate closely with the shift in fast inactivation. Surprisingly, we found that the voltage dependence of inactivation of Nav 1.4 was similar to that of Nav 1.5 in skeletal muscle in vivo. In severely affected fibres, inactivation of both Nav 1.4 and Nav 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 Nav 1.4 and Nav 1.5 in vivo contributes to loss of electrical excitability in SD muscle.
- Subjects
MUSCLE diseases; SODIUM channels; ADRENOCORTICAL hormones; DENERVATION; STEROIDS
- Publication
Journal of Physiology, 2004, Vol 559, Issue 3, p813
- ISSN
0022-3751
- Publication type
Article
- DOI
10.1113/jphysiol.2004.062349