HCN channel-mediated neuromodulation can control action potential velocity and fidelity in central axons
- University Leipzig, Germany
- Institute of Science and Technology Austria (IST Austria), Austria
- Max-Planck-Institute for Experimental Medicine, Germany
- Royal Netherlands Academy of Arts and Sciences, Netherlands
- University of Utrecht, Netherlands
Figures
Figure 1 with 1 supplement
Bidirectional modulation of conduction velocity.
(A) Recording configuration of conduction velocity in mossy fibers using a bipolar tungsten stimulation electrode (stim.) and two glass recording electrodes. (B) Example of compound action …
Figure 1—figure supplement 1
ZD7288 does not alter Na+ currents in cMFBs.
(A) Example whole-cell Na+ currents measured under control conditions (30 nM TTX) and in the presence of additional 30 µM ZD7288 elicited by voltage steps from –80 mV to 0 mV. (B) With 30 nM TTX …
Figure 2
Neuromodulators differentially regulate conduction velocity via HCN channels.
(A) Example of compound action potentials recorded in parallel fibers. Each trace is an average of signals recorded over a period of 1 min, before (at −5 min, black line) and after application of …
Figure 3
Cerebellar mossy fiber terminals have a prominent voltage sag.
(A) Two-photon microscopic image of a whole-cell patch-clamp recording from a cMFB (green) filled with the fluorescence dye Atto 488 in an acute cerebellar brain slice of an adult 39-day-old mouse …
Figure 4
HCN channels support high-frequency action potential firing.
(A) Two-photon microscopic image of a whole-cell patch-clamp recording from a cMFB (green) filled with the fluorescent dye Atto 488 in an acute cerebellar brain slice of an adult (43-day-old) mouse …
Figure 5
The passive membrane properties of cMFBs are HCN- and cAMP-dependent.
(A) Example voltage response of cMFBs to small hyperpolarizing current steps. The application of 30 µM ZD7288 eliminated the Ih-mediated voltage sag (left). Adding 1 mM cAMP to the intracellular …
Figure 6 with 1 supplement
HCN2 is uniformly distributed in mossy fiber axons and boutons.
(A) Electron microscopic image showing a cMFB (magenta) labeled for HCN2. Many particles are diffusely distributed along the plasma membrane of the cMFB, some of them being clustered. Arrows mark …
Figure 6—video 1
Reconstructed cMFB with labeled synapses and HCN2 channels.
3D rendering of a part of a reconstructed cMFB (red) with identified synapses (blue) and HCN2 labeled with gold particles (yellow) based on immune-gold electron microscopic images.
Figure 7
HCN channels in cMFB are strongly modulated by cAMP.
(A) Example currents elicited by hyperpolarizing voltage steps (from –70 mV to a voltage between –70 mV and –150 mV). Top, control current, middle, remaining transients in the presence of 30 µM …
Figure 8
Hodgkin-Huxley model describing HCN2 channel gating.
(A) Example of ZD7288-sensitive currents (black) elicited by the illustrated activation (top) and deactivation (bottom) voltage protocols superimposed with mono-exponential fits (magenta). (B) …
Figure 9 with 1 supplement
Mechanism of control of conduction velocity and metabolic costs of HCN channels.
(A) Illustration of the cerebellar mossy fiber model consisting of 15 connected cylindrical compartments representing cMFBs and the myelinated axon. (B) Grand average voltage response (black) and …
Figure 9—figure supplement 1
Impact of depolarization on NaV availability and on conduction velocity in our model of a mossy fiber axon.
(A) To change the resting membrane potential, the potassium equilibrium potential was varied between –120 and –50 mV. In the default model, the experimentally observed resting membrane potential …
Additional files
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Transparent reporting form
- https://doi.org/10.7554/eLife.42766.014
