Modulation of ATP-sensitive K+ channels by internal acidification in insulin-secreting cells

Zheng Fan, Y. Tokuyama, J. C. Makielski

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The effect of intracellular acidification (low pH(i)) on open probability of the ATP-sensitive K+ (K(ATP)) channel was examined in insulin-secretion cells using an inside-out configuration of the patch-clamp technique. In an insulin-secreting cell line β-TC3, K(ATP) single-channel currents (I(K(ATP))) were readily recorded in the absence of internal ATP. ATP (50 μM and 0.5 mM) dramatically decreased the channel activity. A step decrease of intracellular pH (pH(i)) from 7.4 to 6.7 or 6.3 in the presence of ATP gradually increased the channel activity. In addition, low pH(i) in the presence of ATP could partially restore channel activity lost in a process called 'rundown.' Kinetic analysis revealed a change in channel gating at low pH(i) with ATP. The bursting durations of I(K(ATP))) at pH(i) 6.3 in the presence of ATP were significantly longer than those at pH(i) 7.4 in the absence of ATP. These results suggest that the increased channel activity at low pH(i) might have resulted from a mechanism involving an alteration of channel conformation. We also observed an inhibitory effect of low pH(i) on channel activity. However, the inhibitory effect was much more apparent at pH(i) 5.7 and was only partially reversible. The activation effect of low pH(i) on I(K(ATP))) in the presence of ATP was also observed in acutely isolated rat islet cells and in another insulin-secretion cell line RINm5F, although the effect was weaker and was variable among experiments. We conclude that, as in frog skeletal muscle and cardiac muscle, an increase in channel activity at low pH(i) is one of the mechanisms underlying proton modulation of I(K(ATP))) in insulin-secreting cells.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume267
Issue number4 37-4
StatePublished - 1994
Externally publishedYes

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Acidification
Insulin-Secreting Cells
Adenosine Triphosphate
Modulation
Insulin
Muscle
Cells
Cell Line
Clamping devices
Patch-Clamp Techniques
Islets of Langerhans
Anura
Conformations
Protons
Rats

All Science Journal Classification (ASJC) codes

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Modulation of ATP-sensitive K+ channels by internal acidification in insulin-secreting cells. / Fan, Zheng; Tokuyama, Y.; Makielski, J. C.

In: American Journal of Physiology - Cell Physiology, Vol. 267, No. 4 37-4, 1994.

Research output: Contribution to journalArticle

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