The relationship between potassium(ATP) channels and energy state in skeletal muscle during fatigue development

Abstract

The objective of this study was to test the hypothesis that "During fatigue development there is greater ATP utilization in the absence than in the presence of KATP channel activity". Flexor digitorum brevis (FDB) muscle bundles were fatigued with one tetanic contraction every sec for 3 min. KATP channel activity was abolished pharmacologically using glibenclamide or genetically using Kir6.2-/- FDB muscle bundles; pinacidil was used to activate the channel. Abolishing KATP channel activity had no effect on the decrease in phosphocreatine (PCr), but pinacidil significantly reduced its depletion. Kir6.2-/- FDB showed greater and faster ATP depletion compared to wild type control, but glibenclamide did not reproduce the effect. In the presence of pinacidil ATP content remained significantly above that of control wild type. Unexpectedly Kir6.2-/- FDB muscles generated less lactate than those of wild type. During the first half of the fatigue period, lactate production in wild type FDB were unexpectedly in the order of pinacidil > control > glibenclamide, with the reverse order for the second half of the fatigue period. In conclusion, not all the data supported the hypothesis because the effects of modulating KATP channel activity appeared complicated by difference between acute (pharmacological) and chronic (genetical) approaches, such as changes in ATP and lactate; as well as by time dependent effects, such as observed with lactate.