Activation of ATP-Dependent K$^{+}$ Currents in Intact Skeletal Muscle Fibres by Reduced Intracellular pH

We have used three-microelectrode voltage clamp in conjunction with the ammonium prepulse method to investigate the effects of lowered intracellular pH (pHi) on resting potassium currents of frog skeletal muscle fibres. Potassium currents were recorded in 40 mm K+, Cl--free solution in response eith...

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Published in:Proceedings of the Royal Society. B, Biological sciences Biological sciences, 1992-03, Vol.247 (1320), p.195-198
Main Authors: Standen, N. B., Pettit, A. I., Davies, N. W., Stanfield, P. R.
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - metabolism
Animals
Electric current
Electric potential
Fibric acids
Glyburide - pharmacology
Hydrogen-Ion Concentration
In Vitro Techniques
Intracellular Fluid - metabolism
Muscle fibers
Muscles
Muscles - drug effects
Muscles - metabolism
Potassium
Potassium - metabolism
Potassium channels
Potassium Channels - drug effects
Potassium Channels - metabolism
Quaternary ammonium compounds
Rana temporaria
Skeletal muscle
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Summary:We have used three-microelectrode voltage clamp in conjunction with the ammonium prepulse method to investigate the effects of lowered intracellular pH (pHi) on resting potassium currents of frog skeletal muscle fibres. Potassium currents were recorded in 40 mm K+, Cl--free solution in response either to voltage steps or ramps. An ammonium prepulse (2 h) reduced pHi to 6.45 from a control value of 7.19. The intracellular ATP concentration, measured with high-pressure liquid chromatography (HPLC), was unchanged by this procedure. Mean outward potassium currents were larger in low pHi than in control fibres, being about twice as large at + 40 mV, whereas mean inward currents were very similar in control and low-pHi fibres. The sulphonylurea glibenclamide blocked single KATP channels in excised patches with a Kd of 3 µm. In intact fibres 50 µm glibenclamide had no effect on K+ currents in controls but reduced currents in low-pHi fibres. In the presence of glibenclamide, K+ currents in low-pHi fibres were not significantly different from those in control fibres. We suggest that reduced pHi in intact skeletal muscle fibres opens ATP-dependent potassium channels (KATP channels), as has been shown to occur in excised patches of membrane.
ISSN:0962-8452
1471-2954
DOI:10.1098/rspb.1992.0028