Cell Reports
Volume 27, Issue 8, 21 May 2019, Pages 2249-2261.e7
Journal home page for Cell Reports

Report
Transient, Consequential Increases in Extracellular Potassium Ions Accompany Channelrhodopsin2 Excitation

https://doi.org/10.1016/j.celrep.2019.04.078Get rights and content
Under a Creative Commons license
open access

Highlights

  • Multiple approaches reveal transient K+ elevations during ChR2 excitation

  • ChR2-mediated K+ elevations increase neuronal excitability and cFos expression

  • Neuronal effects of K+ are recapitulated with a model and in vivo

  • Increased K+ may contribute to astrocyte experiments employing ChR2 in vivo

Summary

Channelrhodopsin2 (ChR2) optogenetic excitation is widely used to study neurons, astrocytes, and circuits. Using complementary approaches in situ and in vivo, we found that ChR2 stimulation leads to significant transient elevation of extracellular potassium ions by ∼5 mM. Such elevations were detected in ChR2-expressing mice, following local in vivo expression of ChR2(H134R) with adeno-associated viruses (AAVs), in different brain areas and when ChR2 was expressed in neurons or astrocytes. In particular, ChR2-mediated excitation of striatal astrocytes was sufficient to increase medium spiny neuron (MSN) excitability and immediate early gene expression. The effects on MSN excitability were recapitulated in silico with a computational MSN model and detected in vivo as increased action potential firing in awake, behaving mice. We show that transient, physiologically consequential increases in extracellular potassium ions accompany ChR2 optogenetic excitation. This coincidental effect may be important to consider during astrocyte studies employing ChR2 to interrogate neural circuits and animal behavior.

Keywords

potassium
astrocyte
striatum
neuron
circuit
optogenetics
channelrhodopsin

Cited by (0)

8

These authors contributed equally

9

Lead Contact