Wang2008 - Mimicking the inhibitory effect of riluzole on membrane conductance in skeletal fibres

Wang2008 - Mimicking the inhibitory effect of
riluzole on membrane conductance in skeletal fibres

This model is described in the article:

Riluzole-induced block of
voltage-gated Na+ current and activation of BKCa channels in
cultured differentiated human skeletal muscle cells.

Wang YJ, Lin MW, Lin AA, Wu
SN.
Life Sci. 2008 Jan; 82(1-2):
11-20
Abstract:

Riluzole is known to be of therapeutic use in the management
of amyotrophic lateral sclerosis. In this study, we
investigated the effects of riluzole on ion currents in
cultured differentiated human skeletal muscle cells (dHSkMCs).
Western blotting revealed the protein expression of
alpha-subunits for both large-conductance Ca2+-activated K+
(BK(Ca)) channel and Na+ channel (Na(v)1.5) in these cells.
Riluzole could reduce the frequency of spontaneous beating in
dHSkMCs. In whole-cell configuration, riluzole suppressed
voltage-gated Na+ current (I(Na)) in a concentration-dependent
manner with an IC50 value of 2.3 microM. Riluzole (10 microM)
also effectively increased Ca2+-activated K+ current (I(K(Ca)))
which could be reversed by iberiotoxin (200 nM) and paxilline
(1 microM), but not by apamin (200 nM). In inside-out patches,
when applied to the inside of the cell membrane, riluzole (10
microM) increased BK(Ca)-channel activity with a decrease in
mean closed time. Simulation studies also unraveled that both
decreased conductance of I(Na) and increased conductance of
I(K(Ca)) utilized to mimic riluzole actions in skeletal muscle
cells could combine to decrease the amplitude of action
potentials and increase the repolarization of action
potentials. Taken together, inhibition of I(Na) and stimulation
of BK(Ca)-channel activity caused by this drug are partly, if
not entirely, responsible for its muscle relaxant actions in
clinical setting.

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