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Effects of intracellular pH on ATP‐sensitive K+ channels in mouse pancreatic beta‐cells.
Author(s) -
Proks P,
Takano M,
Ashcroft F M
Publication year - 1994
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1994.sp020047
Subject(s) - intracellular , intracellular ph , chemistry , biophysics , beta (programming language) , microbiology and biotechnology , endocrinology , medicine , biochemistry , biology , computer science , programming language
1. The effects of intracellular pH (pHi) on the ATP‐sensitive K+ channel (K+ATP channel) from mouse pancreatic beta‐cells were examined in inside‐out patches exposed to symmetrical 140 mM K+ solutions. 2. The relationship between channel activity and pHi was described by the Hill equation with half‐maximal inhibition (Ki) at pHi 6.25 and a Hill coefficient of 3.7. 3. Following exposure to pHi < 6.8, channel activity did not recover to its original level. Subsequent application of trypsin to the intracellular membrane surface restored channel activity to its initial level or above. 4. At ‐60 mV the relationship between pHi and the single‐channel current amplitude was described by a modified Hill equation with a Hill coefficient of 2.1, half‐maximal inhibition at pHi 6.48 and a maximum inhibition of 18.5%. 5. A decrease in pHi reduced the extent of channel inhibition by ATP: Ki was 18 microM at pH 7.2 and 33 microM at pH 6.4. The Hill coefficient was also reduced, being 1.65 at pH 7.2 and 1.17 at pH 6.4. 6. When channel activity was plotted as a function of ATP4‐ (rather than total ATP) there was no effect of pHi on the relationship. This suggests that ATP4‐ is the inhibitory ion species and that the effects of reducing pHi are due to the lowered concentration of ATP4‐. 7. Changes in external pH had little effect on either single‐channel or whole‐cell K+ATP currents. 8. The effects of pHi do not support a role for H+ in linking glucose metabolism to K+ATP channel inhibition in pancreatic beta‐cells.