Invited Review: Redox modulation of skeletal muscle contraction: what we know and what we don't

Over the past decade, reactive oxygen species (ROS) and nitric oxide (NO) d erivatives have been established as physiological modulators of skeletal mu scle function. This mini-review addresses the roles of these molecules as e ndogenous regulators of muscle contraction. The article is organized in two parts. First, established concepts are briefly outlined. This section prov ides an overview of ROS production by muscle, antioxidant buffers that oppo se ROS effects, enzymatic synthesis of NO in muscle, the effects of endogen ous ROS on contractile function, and NO as a contractile modulator. Second, a selected group of unresolved topics are highlighted. These more controve rsial issues include putative source(s) of regulatory ROS, the relative imp ortance of the two NO synthase isoforms constitutively coexpressed by muscl e fibers, molecular mechanisms of ROS and NO action, and the physiological relevance of redox regulation. By discussing current questions, as well as the established paradigm, this article is intended to further debate and st imulate research in this area.