Cholesterol intake and statin use regulate neuronal G protein-gated inwardly rectifying potassium channels

Anna Bukiya, Paul S. Blank, Avia Rosenhouse-Dantsker

Research output: Contribution to journalArticle

Abstract

Cholesterol, a critical component of the cellular plasma membrane, is essential for normal neuronal function. Cholesterol content is highest in the brain, where most cholesterol is synthesized de novo; HMG-CoA reductase controls the synthesis rate. Despite strict control, elevated blood cholesterol levels are common and are associated with various neurological disorders. G protein-gated inwardly rectifying potassium (GIRK) channels mediate the actions of inhibitory brain neurotransmitters. Loss of GIRK function enhances neuron excitability; gain of function reduces neuronal activity. However, the effect of dietary cholesterol or HMG-CoA reductase inhibition (i.e., statin therapy) on GIRK function remains unknown. Using a rat model, we compared the effects of a high-cholesterol versus normal diet both with and without atorvastatin, a widely prescribed HMG-CoA reductase inhibitor, on neuronal GIRK currents. The high-cholesterol diet increased hippocampal CA1 region cholesterol levels and correspondingly increased neuronal GIRK currents. Both phenomena were reversed by cholesterol depletion in vitro. Atorvastatin countered the high-cholesterol diet effects on neuronal cholesterol content and GIRK currents; these effects were reversed by cholesterol enrichment in vitro. Our findings suggest that high-cholesterol diet and atorvastatin therapy affect ion channel function in the brain by modulating neuronal cholesterol levels.—Bukiya, A. N., P. S. Blank, and A. Rosenhouse-Dantsker. Cholesterol intake and statin use regulate neuronal G protein-gated inwardly rectifying potassium channels. J. Lipid Res. 2019. 60: 19–29.

Original languageEnglish (US)
Pages (from-to)19-29
Number of pages11
JournalJournal of lipid research
Volume60
Issue number1
DOIs
StatePublished - Jan 1 2019

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Inwardly Rectifying Potassium Channel
Hydroxymethylglutaryl-CoA Reductase Inhibitors
GTP-Binding Proteins
Cholesterol
Nutrition
Hydroxymethylglutaryl CoA Reductases
Brain
Diet
G Protein-Coupled Inwardly-Rectifying Potassium Channels
Diet Therapy
Dietary Cholesterol
Hippocampal CA1 Region
Hypercholesterolemia
Nervous System Diseases
Ion Channels
Cell membranes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

Cholesterol intake and statin use regulate neuronal G protein-gated inwardly rectifying potassium channels. / Bukiya, Anna; Blank, Paul S.; Rosenhouse-Dantsker, Avia.

In: Journal of lipid research, Vol. 60, No. 1, 01.01.2019, p. 19-29.

Research output: Contribution to journalArticle

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