Elsevier

Kidney International

Volume 48, Issue 4, October 1995, Pages 1167-1179
Kidney International

Genetics and Channel Regulation
Effects of phosphorylation on ion channel function

https://doi.org/10.1038/ki.1995.400Get rights and content
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There is considerable evidence suggesting that intracellular second messengers can modulate the activity of ion channels, and that protein phosphorylation by the different protein kinases is a frequent intermediary in these modulatory effects. This conclusion, namely, that ion channel proteins are indeed substrates for phosphorylation, has been verified in numerous biochemical studies [reviewed in 1–6].

The functional correlates of channel phosphorylation are known to involve a change in channel open probability and, in the case of voltage-sensitive ion channels, a shift in the voltage dependence of channel activation. The voltage dependence of ion channel gating appears to be governed by movement of charge in the voltage-sensing moiety. Analogous to alterations in enzyme activities following biochemical modification, phosphorylation of ion channel proteins may lead to conformational changes that subsequently alter their gating and/or conductive properties, giving rise to the observed changes in electrical activity. However, in many cases, it is not yet clear whether it is the ion channels themselves that are directly modified, or whether phosphorylation is simply an early step in a cascade of events that leads ultimately to modulation of channel activity. The development and application of single-channel recording techniques in membrane patches and in artificial planar lipid bilayers has provided a means to investigate the effects of phosphorylation on the kinetic properties of ion channels. Moreover, the recent application of site directed mutagenesis to cloned ion channels has pinpointed specific amino acid residues critical for the specific kinase effects.

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