Similarity of ATP-dependent K+ channels in skeletal muscle fibres from normal and mutant mdx mice.

摘要

1. ATP-dependent K+ (KATP) channels were studied in fibres isolated from flexor digitorum brevis and interosseal skeletal muscles of normal and mutant mdx mice using the patch clamp technique in the presence of asymmetrical K+ concentrations (5 mM K+ in the pipette and in vivo intracellular [K+] or 145 mM K+ at the cytoplasmic face). 2. In cell-attached patches from mdx muscle fibres bathed in K(+)-rich solution, cell poisoning with fluorodinitrobenzene induced partially reversible opening of channels carrying an outward current of an amplitude of 1.2 pA at 0 mV. Exposure of fibres to the K+ channel opener cromakalim led to opening of the same type of channel. These channels were assumed to be KATP channels. 3. On excision of inside-out patches from mdx muscle fibres, in the absence of intracellular ATP, KATP channels were active: they carried a unitary outward current of 1.6 pA at 0 mV and were inhibited by intracellular ATP and glibenclamide. The number of KATP channels per patch was not significantly different in muscles from normal and mdx mice. 4. In inside-out patches, in the presence of 1 mM intracellular Mg2+, slope conductances of 21 and 20.3 pS were found for KATP channels in normal and mdx muscle, respectively. In the absence of Mg2+, slope conductances of KATP channels were 31.3 and 32 pS in normal and mdx muscle, respectively and KATP channel activity was augmented in mdx muscle in the same way as in normal muscle. Activity of the same KATP channel was observed in extensor digitorum longus muscle from normal and mdx mice. 5. In inside-out patches held at 0 mV, the relationship between KATP channel activity and intracellular ATP was described by a Hill equation: Ki values were 23 and 21 microM and Hill coefficients were 1.8 and 1.9 in normal and mdx muscle, respectively. 6. These results indicate that the distribution, the conductance properties and ATP sensitivity of KATP channels do not differ in normal and in mdx mouse skeletal muscle.