Referenced in: none

Automatically associated channels: Kv7.2

Title: Coordinated signal integration at the M-type potassium channel upon muscarinic stimulation.

Authors: Anastasia Kosenko, Seungwoo Kang, Ida M Smith, Derek L Greene, Lorene K Langeberg, John D Scott, Naoto Hoshi

Journal, date & volume: , 2012 May 29 , ,

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22643219

Abstract
Several neurotransmitters, including acetylcholine, regulate neuronal tone by suppressing a non-inactivating low-threshold voltage-gated potassium current generated by the M-channel. Agonist dependent control of the M-channel is mediated by calmodulin, activation of anchored protein kinase C (PKC), and depletion of the phospholipid messenger phosphatidylinositol 4,5-bisphosphate (PIP2). In this report, we show how this trio of second messenger responsive events acts synergistically and in a stepwise manner to suppress activity of the M-current. PKC phosphorylation of the KCNQ2 channel subunit induces dissociation of calmodulin from the M-channel complex. The calmodulin-deficient channel has a reduced affinity towards PIP2. This pathway enhances the effect of concomitant reduction of PIP2, which leads to disruption of the M-channel function. These findings clarify how a common lipid cofactor, such as PIP2, can selectively regulate ion channels.