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BK channels modulate pre- and postsynaptic signaling at reciprocal synapses in retina

Nature Neuroscience volume 12, pages 585–592 (2009)Cite this article

Abstract

In the mammalian retina, A17 amacrine cells provide reciprocal inhibitory feedback to rod bipolar cells, thereby shaping the time course of visual signaling in vivo. Previous results have indicated that A17 feedback can be triggered by Ca2+ influx through Ca2+-permeable AMPA receptors and can occur independently of voltage-gated Ca2+ (Cav) channels, whose presence and functional role in A17 dendrites have not yet been explored. We combined electrophysiology, calcium imaging and immunohistochemistry and found that L-type Cav channels in rat A17 amacrine cells were located at the sites of reciprocal synaptic feedback and that their contribution to GABA release was diminished by large-conductance Ca2+-activated potassium (BK) channels, which suppress postsynaptic depolarization in A17s and limit Cav channel activation. We also found that BK channels, by limiting GABA release from A17s, regulate the flow of excitatory synaptic transmission through the rod pathway.

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Figure 1: Voltage-gated calcium channels are colocalized with synaptic inputs at individual A17 varicosities.
Figure 2: Functional L-type voltage-gated calcium channels are expressed at A17 synaptic varicosities and somata.
Figure 3: Intracellular stores amplify voltage-dependent calcium responses in varicosities.
Figure 4: A17s varicosities express rapidly inactivating BK channels that are functionally coupled to L-type voltage-gated calcium channels.
Figure 5: BK channels suppress synaptic transmission.
Figure 6: BK channel–modulated Cav channels enhance GABA release from A17s.
Figure 7: Modification of AMPAR kinetics with cyclothiazide recruits Cav channel–dependent enhancement of GABA release.
Figure 8: BK channels in A17 amacrine cells modulate feedforward excitatory signaling at the RBC dyad.

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Acknowledgements

We thank C. McBain for critically reading the manuscript, members of the Diamond and Isaac laboratories for helpful discussions and E. Compton-Daw for assistance with spectrophotometry. This work was supported by the US National Institute of Neurological Disorders and Stroke Intramural Research Program.

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Author notes

  1. Andrés E Chávez

    Present address: Present address: Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, USA.,

Authors and Affiliations

  1. Synaptic Physiology Section, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA

    William N Grimes, Andrés E Chávez & Jeffrey S Diamond

  2. University of Maryland/NIH Biophysics Graduate Partnership Program, College Park/Bethesda, Maryland, USA

    William N Grimes

  3. Unit on Retinal Neurophysiology, National Eye Institute, Bethesda, Maryland, USA

    Wei Li

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Contributions

W.N.G. conducted the electrophysiological and two-photon imaging experiments. W.L. carried out the immunohistochemistry experiments. A.E.C. performed preliminary electrophysiological experiments contributing to the formulation of the project. W.N.G., A.E.C. and J.S.D. designed the experiments. W.N.G. and J.S.D. wrote the manuscript.

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Correspondence to Jeffrey S Diamond.

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Grimes, W., Li, W., Chávez, A. et al. BK channels modulate pre- and postsynaptic signaling at reciprocal synapses in retina. Nat Neurosci 12, 585–592 (2009). https://doi.org/10.1038/nn.2302

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