Modulation of single Ca2+-dependent K+-channel activity by protein phosphorylation

Abstract

There is considerable evidence that cyclic AMP can modulate the electrical activity of excitable cells1–10 and that protein phosphorylation by the catalytic subunit (CS) of cAMP-dependent protein kinase is a necessary step in these modulatory effects11–21. In analogy to alterations in enzyme activities following phosphorylation12, it seems possible that direct phosphorylation of ion-channel proteins may alter their gating properties, giving rise to the observed changes in electrical activity. However, the results obtained so far do not indicate whether it is ion channels themselves that are phosphorylated, or whether phosphorylation is simply an early step in some cascade of events which leads ultimately to modulation of channel activity. The development of single-channel recording techniques22 has provided a way to investigate this question. Here we describe effects of CS on the activity of individual Ca2+-dependent K+ channels from the nervous system of the land snail Helix measured in isolated membrane patches and in artificial phospholipid bilayers. The results demonstrate that cAMP-dependent protein phosphorylation produces long-lasting changes in the activity of individual channels, and indicate that the relevant phosphorylation site is closely associated with the channel.

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Ewald, D., Williams, A. & Levitan, I. Modulation of single Ca2+-dependent K+-channel activity by protein phosphorylation. Nature 315, 503–506 (1985). https://doi.org/10.1038/315503a0

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