CaM kinase II phosphorylation of slo Thr107 regulates activity and ethanol responses of BK channels

Jianxi Liu, Maria Asuncion-Chin, Pengchong Liu, Alejandro Dopico

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

High-conductance, Ca2+-activated and voltage-gated (BK) channels set neuronal firing. They are almost universally activated by alcohol, leading to reduced neuronal excitability and neuropeptide release and to motor intoxication. However, several BK channels are inhibited by alcohol, and most other voltage-gated K+ channels are refractory to drug action. BK channels are homotetramers (encoded by Slo1) that possess a unique transmembrane segment (SO), leading to a cytosolic S0-S1 loop. We identified Thr107 of bovine slo (bslo) in this loop as a critical residue that determines BK channel responses to alcohol. In addition, the activity of Ca2+/calmodulin- dependent protein kinase II (CaMKII) in the cell controlled channel activity and alcohol modulation. Incremental CaMKII-mediated phosphorylation of Thr107 in the BK tetramer progressively increased channel activity and gradually switched the channel alcohol responses from robust activation to inhibition. Thus, CaMKII phosphorylation of slo Thr107 works as a 'molecular dimmer switch' that could mediate tolerance to alcohol, a form of neuronal plasticity.

Original languageEnglish (US)
Pages (from-to)41-49
Number of pages9
JournalNature Neuroscience
Volume9
Issue number1
DOIs
StatePublished - Jan 1 2006

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Large-Conductance Calcium-Activated Potassium Channels
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Ethanol
Phosphorylation
Alcohols
Voltage-Gated Potassium Channels
Neuronal Plasticity
Neuropeptides
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

CaM kinase II phosphorylation of slo Thr107 regulates activity and ethanol responses of BK channels. / Liu, Jianxi; Asuncion-Chin, Maria; Liu, Pengchong; Dopico, Alejandro.

In: Nature Neuroscience, Vol. 9, No. 1, 01.01.2006, p. 41-49.

Research output: Contribution to journalArticle

Liu, Jianxi ; Asuncion-Chin, Maria ; Liu, Pengchong ; Dopico, Alejandro. / CaM kinase II phosphorylation of slo Thr107 regulates activity and ethanol responses of BK channels. In: Nature Neuroscience. 2006 ; Vol. 9, No. 1. pp. 41-49.
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