Two-pore potassium ion channels are inhibited by both Gq/11- and Gi-coupled P2Y receptors

Shakya-Shrestha, S. and Parmar, M. and Kennedy, Charles and Bushell, T. (2010) Two-pore potassium ion channels are inhibited by both Gq/11- and Gi-coupled P2Y receptors. Molecular and Cellular Neuroscience, 43 (4). pp. 363-369. ISSN 1044-7431

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Abstract

Two-pore potassium (K2P) ion channels and P2Y receptors modulate the activity of neurones and are targets for the treatment of neuronal disorders. Here we have characterised their interaction. In cells coexpressing the Gαi-coupled hP2Y12 receptor, ADP and ATP significantly inhibited hK2P2.1 currents. This was abolished by pertussis toxin (PTX), the hP2Y12 antagonist AR-C69931MX, the hP2Y1 antagonist MRS2179 and by mutating potential PKA/PKC phosphorylation sites in the channel C terminal. In cells coexpressing the Gαq/11-coupled hP2Y1 receptor, ADP and ATP also inhibited hK2P2.1 currents, which were abolished by MRS2179, but unaffected by AR-C69931MX and PTX. When both receptors were coexpressed with K2P2.1 channels, ADP-induced inhibition was antagonised by AR-C69913MX and MRS2179, but not PTX. Thus, both Gαq/11- and Gαi-coupled P2Y receptors inhibit K2P channels and the action of hP2Y12 receptors appears to involve co-activation of endogenous hP2Y1 receptors. This represents a novel mechanism by which P2Y receptors may modulate neuronal activity.

ORCID iDs

Shakya-Shrestha, S., Parmar, M., Kennedy, Charles ORCID logoORCID: https://orcid.org/0000-0001-9661-5437 and Bushell, T. ORCID logoORCID: https://orcid.org/0000-0003-4145-9670;