A K-ATP channel deficiency affects resting tension, not contractile force,during fatigue in skeletal muscle

The objective of this study was to determine how an ATP-sensitive K+ (K-ATP ) channel deficiency affects the contractile and fatigue characteristics of extensor digitorum longus (EDL) and soleus muscle of 2- to 3-mo-old and 1- yr-old mice. K-ATP channel-deficient mice were obtained by disrupting the K ir6.2 gene that encodes for the protein forming the pore of the channel. At 2-3 mo of age, the force-frequency curve, the twitch, and the tetanic forc e of EDL and soleus muscle of K-ATP channel-deficient mice were not signifi cantly different from those in wild-type mice. However, the tetanic force a nd maximum rate of force development decreased with aging to a greater exte nt in EDL and soleus muscle of K-ATP channel-deficient mice (24-40%) than i n muscle of wild-type mice (7-17%). During fatigue, the K-ATP channel defic iency had no effect on the decrease in tetanic force in EDL and soleus musc le, whereas it caused a significantly greater increase in resting tension w hen compared with muscle of wild-type mice. The recovery of tetanic force a fter fatigue was not affected by the deficiency in 2- to 3-mo-old mice, whe reas in 1-yr-old mice, force recovery was significantly less in muscle of K -ATP channel-deficient than wild-type mice. It is suggested that the major function of the K-ATP channel during fatigue is to reduce the development o f a resting tension and not to contribute to the decrease in force. It is a lso suggested that the K-ATP channel plays an important role in protecting muscle function in older mice.