Mitochondrial K_ATP channels in skeletal muscle: are protein kinases C and G, and nitric oxide synthase involved in the fatigue process?

Abstract

Background:

Fatigue in skeletal muscle is defined as a reduction in the physical power needed to execute a function or as an inability to maintain mitochondrial ATP production. The mitochondrial potassium channel (mitoK_ATP) participates in combating fatigue in skeletal muscle. In this work, we evaluated the role of the mitoK_ATP channel activator (diazoxide) and inhibitors of the signaling routes (protein kinase C, staurosporine; protein kinase G, KT5823; and nitric oxide synthase, metil N^G-Nitro-L-arginine ester, L-NAME), on muscle fatigue tension. In addition, we evaluated the main signaling routes used by the nitric oxide synthase protein and protein kinase C and G, in the presence of their specific activators.

Methods:

We used the anterior latissimus dorsi skeletal muscle of 2–3-week-old chicks. This muscle consists of slow muscle fibers. Tension was achieved by applying repetitive electrical stimulation that induced fatigue in an in vitro model.

Results:

Diazoxide significantly reduced muscle fatigue (P = 0.0002 in peak tension, P = 0.000002 in maximum tension) by increasing post-fatigue tension, in spite of the fact that 5-hydroxydecanoate, a selective inhibitor of mitoK_ATP, did not suppress post-fatigue tension.

Conclusion:

Our results suggest a lack of direct interaction in inhibition of the signaling routes during fatigue-induced mitoK_ATP activation. This effect is possibly due to the type of skeletal muscle fibers (slow), the stimulation protocols (twitch), and the animal (avian) model used in the study.

Keywords::

• fatigue
• skeletal muscle
• mitochondrial ATP-sensitive potassium channels