Different sulfonylurea and ATP sensitivity characterizes the juvenile and the adult form of K-ATP channel complex of rat skeletal muscle

We have described here the changes of the biophysical and pharmacological properties of the sarcolemmel ATP-sensitive K+ channels (K-ATP) of rat skeletal muscle fibres, occurring from an early postnatal period (5 days) to adulthood (210 days). The age-dependent changes of the mean current of the K-ATP channel (channel activity) and the effects of the blockers, ATP and glybenclamide, were examined by using the patch-clamp technique. Measurements of the single channel conductance, open probability and channel density were also performed. Excision of cell-attached patches into an ATP-free solution dramatically increased the K-ATP channel activity; however, the intensity of this activity was age dependent. The relative activity was low at 5-6 days of postnatal life, increased to a plateau at 12-13 days, then declined toward adult values after 37 days. Two distinct types of the K-ATP channel complex could be distinguished. The early developmental period (5-6 days) was dominated by a K-ATP channel having a conductance of 66 pS, a high open probability of 0.602, and an IC50 for ATP and glybenclamide of 123.1 mu M and 3.97 mu M respectively. This type of channel disappeared with maturation of the muscle to be replaced by the adult form of the K-ATP channel. The latter developmental period (from 56 days) was dominated by a K-ATP channel having a 71 pS conductance, but a low open probability of 0.222. This adult channel was also 3.2 and 73.5 times more sensitive to ATP and glybenclamide, respectively. We have also observed that the sensitivity of the K-ATP channel to ATP and glybenclamide develops differently. Indeed, the greater increase in the sensitivity of the channel to ATP was observed between 5 and 12 days of age. Conversely, the greater enhancement of the sensitivity of the channel to glybenclamide occurred between 12 and 37 days. A further increase of this parameter was also observed between 37 and 56 days of age. The differential age-dependent acquisition of the sensitivity of K-ATP channels to ATP and glybenclamide poses the hypothesis that in rat skeletal muscle the ATP regulatory site and sulfonylurea site are located on different subunits of the K-ATP channel complex. The intense K-ATP channel activity recorded between 12 and 37 days of postnatal life sustains the high resting macroscopic K+ conductance characteristic of the early postnatal development.